Recurrent pregnancy loss (RPL) is an obstetrical complication that affects about 3% of reproductive age couples. Genetic and non-genetic causes of RPL are multiple; however, aneuploidy is the most common obstetrical complication that can explain single and recurrent pregnancy loss (present in about 60% of recognized clinical pregnancies which result in a miscarriage). Parental karyotyping will only be of potential benefit for 2 to 5 percentage of RPL couples who are translocation carriers. Products of conception (POC) karyotype analysis has been used to direct management in RPL and has been shown to be cost-effective, but the technique has many limitations including high culture failure rate and maternal cell contamination. These limitations can be significantly reduced using POC chromosomal microarray (CMA) technology. We believe that POC genetic testing should be performed after the second and subsequent pregnancy loss using CMA. Although the results will not generally alter the course of treatment, the knowledge of the reason for the loss is of great emotional comfort to many patients. In addition, POC CMA performed in conjunction with a regular complete maternal RPL work-up will identify the group of truly unexplained RPL. Thus, only 10% of patients with RPL will complete an evaluation having a euploid loss and an otherwise normal work-up. This group of "truly unexplained RPL" would be ideal for new research trials and therapies. Pre-implantation genetic testing (PGT) technology has improved recently with day 5 trophectoderm biopsy as compared to biopsy on day 3 as well as with the addition of CMA and next-generation sequencing technologies. The most recent studies on PGT-SR (PGT-Structural rearrangement) show improved clinical and live birth rates per pregnancy, as well as decreased miscarriage rate for translocation carriers. PGT-A (PGT-aneuploidy) may have a limited role in RPL in cases with documented recurrent POC aneuploidy.
{"title":"Genetic Testing for Aneuploidy in Patients Who Have Had Multiple Miscarriages: A Review of Current Literature.","authors":"Ralph S Papas, William H Kutteh","doi":"10.2147/TACG.S320778","DOIUrl":"10.2147/TACG.S320778","url":null,"abstract":"<p><p>Recurrent pregnancy loss (RPL) is an obstetrical complication that affects about 3% of reproductive age couples. Genetic and non-genetic causes of RPL are multiple; however, aneuploidy is the most common obstetrical complication that can explain single and recurrent pregnancy loss (present in about 60% of recognized clinical pregnancies which result in a miscarriage). Parental karyotyping will only be of potential benefit for 2 to 5 percentage of RPL couples who are translocation carriers. Products of conception (POC) karyotype analysis has been used to direct management in RPL and has been shown to be cost-effective, but the technique has many limitations including high culture failure rate and maternal cell contamination. These limitations can be significantly reduced using POC chromosomal microarray (CMA) technology. We believe that POC genetic testing should be performed after the second and subsequent pregnancy loss using CMA. Although the results will not generally alter the course of treatment, the knowledge of the reason for the loss is of great emotional comfort to many patients. In addition, POC CMA performed in conjunction with a regular complete maternal RPL work-up will identify the group of truly unexplained RPL. Thus, only 10% of patients with RPL will complete an evaluation having a euploid loss and an otherwise normal work-up. This group of \"truly unexplained RPL\" would be ideal for new research trials and therapies. Pre-implantation genetic testing (PGT) technology has improved recently with day 5 trophectoderm biopsy as compared to biopsy on day 3 as well as with the addition of CMA and next-generation sequencing technologies. The most recent studies on PGT-SR (PGT-Structural rearrangement) show improved clinical and live birth rates per pregnancy, as well as decreased miscarriage rate for translocation carriers. PGT-A (PGT-aneuploidy) may have a limited role in RPL in cases with documented recurrent POC aneuploidy.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2021-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/18/tacg-14-321.PMC8315809.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39257922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-14eCollection Date: 2021-01-01DOI: 10.2147/TACG.S318884
Son Trinh The, Sang Trieu Tien, Tam Vu Van, Nhat Nguyen Ngoc, My Tran Ngoc Thao, Khoa Tran Van, Dinh Vu Nhat, Binh Do Nhu
Background: Adrenoleukodystrophy (ALD) is a rare sex-linked recessive disorder that disrupts adrenal gland function and the white matter of the nervous system. According to recent epidemiological statistics, up to this moment, the disease is the most recorded peroxisomal disorder. ABCD1 is a gene related to ALD, with more than 850 unique mutations have been reported. Early diagnosis of the disease would help to consult families with ALD to plan for interventions to prevent passing along the pathogenic mutations to their children.
Material and methods: A heterozygous ABCD1 gene mutation related to ALD found in a Vietnamese woman was used to design primers for the polymerase chain reaction (PCR) to amplify the segment spanning the mutation. Then, combining sequencing methods for the PCR products, especially Sanger sequencing and next-generation sequencing (NGS), a protocol was developed to detect mutations on the ABCD1 gene to apply for the DNA samples of in-vitro fertilization (IVF) embryos biopsied at the blastocyst stage to screen for pathogenic alleles.
Results: The established protocol for PGD of ALD detected mutant alleles in 5/8 embryos (62.5%), while the remaining 3 embryos (37.5%) did not carry any mutation. One of the 3 embryos was transferred, and a healthy female baby was born after a full-term pregnancy.
Conclusion: The developed protocol was helpful for the preimplantation genetic diagnosis process to help families with the monogenic disease of ALD but wish to have healthy children.
{"title":"Successful Pregnancy Following Preimplantation Genetic Diagnosis of Adrenoleukodystrophy by Detection of Mutation on the <i>ABCD1</i> Gene.","authors":"Son Trinh The, Sang Trieu Tien, Tam Vu Van, Nhat Nguyen Ngoc, My Tran Ngoc Thao, Khoa Tran Van, Dinh Vu Nhat, Binh Do Nhu","doi":"10.2147/TACG.S318884","DOIUrl":"https://doi.org/10.2147/TACG.S318884","url":null,"abstract":"<p><strong>Background: </strong>Adrenoleukodystrophy (ALD) is a rare sex-linked recessive disorder that disrupts adrenal gland function and the white matter of the nervous system. According to recent epidemiological statistics, up to this moment, the disease is the most recorded peroxisomal disorder. <i>ABCD1</i> is a gene related to ALD, with more than 850 unique mutations have been reported. Early diagnosis of the disease would help to consult families with ALD to plan for interventions to prevent passing along the pathogenic mutations to their children.</p><p><strong>Material and methods: </strong>A heterozygous <i>ABCD1</i> gene mutation related to ALD found in a Vietnamese woman was used to design primers for the polymerase chain reaction (PCR) to amplify the segment spanning the mutation. Then, combining sequencing methods for the PCR products, especially Sanger sequencing and next-generation sequencing (NGS), a protocol was developed to detect mutations on the <i>ABCD1</i> gene to apply for the DNA samples of in-vitro fertilization (IVF) embryos biopsied at the blastocyst stage to screen for pathogenic alleles.</p><p><strong>Results: </strong>The established protocol for PGD of ALD detected mutant alleles in 5/8 embryos (62.5%), while the remaining 3 embryos (37.5%) did not carry any mutation. One of the 3 embryos was transferred, and a healthy female baby was born after a full-term pregnancy.</p><p><strong>Conclusion: </strong>The developed protocol was helpful for the preimplantation genetic diagnosis process to help families with the monogenic disease of ALD but wish to have healthy children.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2021-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a9/55/tacg-14-313.PMC8286725.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39202762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fragile X syndrome (FXS), is an X-linked inherited genetic disease. FXS is the leading cause of inherited intellectual disability and autism in the world. Those affected are characterized by intellectual disability, language deficit, typical facies, and macroorchidism. Alterations in the FMR1 gene have been associated with FXS. The majority of people with this condition have an allele with an expansion of more than 200 repeats in a tract of CGGs within the 5' untranslated region, and this expansion is associated with a hypermethylated state of the gene promoter. FXS has incomplete penetrance and variable expressivity. Intellectual disability is present in 100% of males and 60% of females. Autism spectrum disorder symptoms appear in 50% to 60% of males and 20% of females. Other characteristics such as behavioral and physical alterations have significant variations in presentation frequency. The molecular causes of the variable phenotype in FXS patients are becoming clear: these causes are related to the FMR1 gene itself and to secondary, modifying gene effects. In FXS patients, size and methylation mosaicisms are common. Secondary to mosaicism, there is a variation in the quantity of FMR1 mRNA and the protein coded by the gene Fragile Mental Retardation Protein (FMRP). Potential modifier genes have also been proposed, with conflicting results. Characterizing patients according to CGG expansion, methylation status, concentration of mRNA and FMRP, and genotypification for possible modifier genes in a clinical setting offers an opportunity to identify predictors for treatment response evaluation. When intervention strategies become available to modulate the course of the disease they could be crucial for selecting patients and identifying the best therapeutic intervention. The purpose of this review is to present the information available about the molecular causes of the variability of the expression incomplete penetrance and variable expressivity in FXS and their potential clinical applications.
{"title":"Variable Expressivity in Fragile X Syndrome: Towards the Identification of Molecular Characteristics That Modify the Phenotype.","authors":"César Payán-Gómez, Julian Ramirez-Cheyne, Wilmar Saldarriaga","doi":"10.2147/TACG.S265835","DOIUrl":"10.2147/TACG.S265835","url":null,"abstract":"<p><p>Fragile X syndrome (FXS), is an X-linked inherited genetic disease. FXS is the leading cause of inherited intellectual disability and autism in the world. Those affected are characterized by intellectual disability, language deficit, typical facies, and macroorchidism. Alterations in the <i>FMR1</i> gene have been associated with FXS. The majority of people with this condition have an allele with an expansion of more than 200 repeats in a tract of CGGs within the 5' untranslated region, and this expansion is associated with a hypermethylated state of the gene promoter. FXS has incomplete penetrance and variable expressivity. Intellectual disability is present in 100% of males and 60% of females. Autism spectrum disorder symptoms appear in 50% to 60% of males and 20% of females. Other characteristics such as behavioral and physical alterations have significant variations in presentation frequency. The molecular causes of the variable phenotype in FXS patients are becoming clear: these causes are related to the <i>FMR1</i> gene itself and to secondary, modifying gene effects. In FXS patients, size and methylation mosaicisms are common. Secondary to mosaicism, there is a variation in the quantity of <i>FMR1</i> mRNA and the protein coded by the gene Fragile Mental Retardation Protein (FMRP). Potential modifier genes have also been proposed, with conflicting results. Characterizing patients according to CGG expansion, methylation status, concentration of mRNA and FMRP, and genotypification for possible modifier genes in a clinical setting offers an opportunity to identify predictors for treatment response evaluation. When intervention strategies become available to modulate the course of the disease they could be crucial for selecting patients and identifying the best therapeutic intervention. The purpose of this review is to present the information available about the molecular causes of the variability of the expression incomplete penetrance and variable expressivity in FXS and their potential clinical applications.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2021-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bc/35/tacg-14-305.PMC8273740.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39186644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-03eCollection Date: 2021-01-01DOI: 10.2147/TACG.S303668
Achmad Headriawan, Alvinsyah Adhityo Pramono, Abdurachman Sukadi, Alex Chairulfatah, Ani Melani Maskoen, Heda Melinda Nataprawira
Background: As pediatric tuberculosis (TB) globally is still reported challenging in diagnosis, to date, a lot of efforts have been established to eliminate the disease including proper treatment regimen using anti-TB drugs. However, antituberculosis drug-induced hepatotoxicity (ADIH) is known to interfere the success of the prescribed therapy. ADIH was found to be correlated with polymorphisms of NAT2 gene, that is responsible to transcript the NAT2 enzyme, a metabolizer of isoniazid (INH). The most common NAT2 gene polymorphisms in Asian population associated with ADIH are rs1041983, rs1799929, rs1799930 and rs1799931. The study aimed to investigate the 4 single nucleotide polymorphisms (SNPs) in pediatric TB that experienced ADIH.
Methods: We conducted a case-control study comparing 31 each of pediatric TB experience with and without ADIH. All pediatric TB was selected from 451 pediatric TB Registry of Respirology Division, Department of Child Health Faculty of Medicine Universitas Padjadjaran/Dr Hasan Sadikin Hospital during January 2016 to July 2018. Genomic DNA PCR and sequencing to identify polymorphisms of rs1041983, rs1799929, rs1799930 and rs1799931 were performed in both groups. Data analysis was performed using the Epi info Ver. 7 software.
Results: Thirty-one pediatric TB experiences with and without ADIH were enrolled in this study. SNP rs1041983 significantly affected the occurrence of ADIH (OR 2.39, CI 95% (1.15-4.96), p=0.019). The rs1799929, rs1799930 and rs1799931 did not significantly affect the occurrence of ADIH (p=0.133, p=0.150 and p=0.659, respectively).
Conclusion: Polymorphism SNP rs1041983 had association with the occurrence of ADIH.
背景:由于全球儿童结核病(TB)的诊断仍然具有挑战性,迄今为止,已经建立了许多努力来消除这种疾病,包括使用抗结核药物的适当治疗方案。然而,已知抗结核药物引起的肝毒性(ADIH)会干扰处方治疗的成功。发现ADIH与NAT2基因多态性相关,该基因负责转录异烟肼(INH)代谢产物NAT2酶。与ADIH相关的亚洲人群中最常见的NAT2基因多态性为rs1041983、rs1799929、rs1799930和rs1799931。该研究旨在探讨儿童结核病ADIH的4个单核苷酸多态性(snp)。方法:我们进行了一项病例对照研究,比较了31名患有和不患有ADIH的儿童结核病患者。所有儿童结核病患者均选自2016年1月至2018年7月期间帕迪贾兰大学医学院/哈桑·萨迪金博士医院儿童健康科呼吸内科451例儿童结核病登记病例。对两组rs1041983、rs1799929、rs1799930和rs1799931进行基因组DNA PCR和测序,鉴定多态性。使用Epi info Ver. 7软件进行数据分析。结果:31名患有或不患有ADIH的儿童结核病患者被纳入本研究。SNP rs1041983显著影响ADIH的发生(OR 2.39, CI 95% (1.15-4.96), p=0.019)。rs1799929、rs1799930和rs1799931对ADIH的发生无显著影响(p=0.133、p=0.150和p=0.659)。结论:多态性SNP rs1041983与ADIH的发生有关。
{"title":"NAT2 Gene rs1041983 is Associated with Anti-Tuberculosis Drug Induced Hepatotoxicity Among Pediatric Tuberculosis in Bandung, Indonesia.","authors":"Achmad Headriawan, Alvinsyah Adhityo Pramono, Abdurachman Sukadi, Alex Chairulfatah, Ani Melani Maskoen, Heda Melinda Nataprawira","doi":"10.2147/TACG.S303668","DOIUrl":"https://doi.org/10.2147/TACG.S303668","url":null,"abstract":"<p><strong>Background: </strong>As pediatric tuberculosis (TB) globally is still reported challenging in diagnosis, to date, a lot of efforts have been established to eliminate the disease including proper treatment regimen using anti-TB drugs. However, antituberculosis drug-induced hepatotoxicity (ADIH) is known to interfere the success of the prescribed therapy. ADIH was found to be correlated with polymorphisms of NAT2 gene, that is responsible to transcript the NAT2 enzyme, a metabolizer of isoniazid (INH). The most common NAT2 gene polymorphisms in Asian population associated with ADIH are rs1041983, rs1799929, rs1799930 and rs1799931. The study aimed to investigate the 4 single nucleotide polymorphisms (SNPs) in pediatric TB that experienced ADIH.</p><p><strong>Methods: </strong>We conducted a case-control study comparing 31 each of pediatric TB experience with and without ADIH. All pediatric TB was selected from 451 pediatric TB Registry of Respirology Division, Department of Child Health Faculty of Medicine Universitas Padjadjaran/Dr Hasan Sadikin Hospital during January 2016 to July 2018. Genomic DNA PCR and sequencing to identify polymorphisms of rs1041983, rs1799929, rs1799930 and rs1799931 were performed in both groups. Data analysis was performed using the Epi info Ver. 7 software.</p><p><strong>Results: </strong>Thirty-one pediatric TB experiences with and without ADIH were enrolled in this study. SNP rs1041983 significantly affected the occurrence of ADIH (OR 2.39, CI 95% (1.15-4.96), p=0.019). The rs1799929, rs1799930 and rs1799931 did not significantly affect the occurrence of ADIH (p=0.133, p=0.150 and p=0.659, respectively).</p><p><strong>Conclusion: </strong>Polymorphism SNP rs1041983 had association with the occurrence of ADIH.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2d/7a/tacg-14-297.PMC8184287.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39002294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-02eCollection Date: 2021-01-01DOI: 10.2147/TACG.S273525
Fabio Coppedè
Premature-ageing syndromes are a heterogeneous group of rare genetic disorders resembling features of accelerated ageing and resulting from mutations in genes coding for proteins required for nuclear lamina architecture, DNA repair and maintenance of genome stability, mitochondrial function and other cellular processes. Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two of the best-characterized progeroid syndromes referred to as childhood- and adulthood-progeria, respectively. This article provides an updated overview of the mutations leading to HGPS, WS, and to the spectrum of premature-ageing laminopathies ranging in severity from congenital restrictive dermopathy (RD) to adult-onset atypical WS, including RD-like laminopathies, typical and atypical HGPS, more and less severe forms of mandibuloacral dysplasia (MAD), Néstor-Guillermo progeria syndrome (NGPS), atypical WS, and atypical progeroid syndromes resembling features of HGPS and/or MAD but resulting from impaired DNA repair or mitochondrial functions, including mandibular hypoplasia, deafness, progeroid features, and lipodystrophy (MDPL) syndrome and mandibuloacral dysplasia associated to MTX2 (MADaM). The overlapping signs and symptoms among different premature-ageing syndromes, resulting from both a large genetic heterogeneity and shared pathological pathways underlying these conditions, require an expert clinical evaluation in specialized centers paralleled by next-generation sequencing of panels of genes involved in these disorders in order to establish as early as possible an accurate clinical and molecular diagnosis for a proper patient management.
{"title":"Mutations Involved in Premature-Ageing Syndromes.","authors":"Fabio Coppedè","doi":"10.2147/TACG.S273525","DOIUrl":"https://doi.org/10.2147/TACG.S273525","url":null,"abstract":"<p><p>Premature-ageing syndromes are a heterogeneous group of rare genetic disorders resembling features of accelerated ageing and resulting from mutations in genes coding for proteins required for nuclear lamina architecture, DNA repair and maintenance of genome stability, mitochondrial function and other cellular processes. Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two of the best-characterized progeroid syndromes referred to as childhood- and adulthood-progeria, respectively. This article provides an updated overview of the mutations leading to HGPS, WS, and to the spectrum of premature-ageing laminopathies ranging in severity from congenital restrictive dermopathy (RD) to adult-onset atypical WS, including RD-like laminopathies, typical and atypical HGPS, more and less severe forms of mandibuloacral dysplasia (MAD), Néstor-Guillermo progeria syndrome (NGPS), atypical WS, and atypical progeroid syndromes resembling features of HGPS and/or MAD but resulting from impaired DNA repair or mitochondrial functions, including mandibular hypoplasia, deafness, progeroid features, and lipodystrophy (MDPL) syndrome and mandibuloacral dysplasia associated to <i>MTX2</i> (MADaM). The overlapping signs and symptoms among different premature-ageing syndromes, resulting from both a large genetic heterogeneity and shared pathological pathways underlying these conditions, require an expert clinical evaluation in specialized centers paralleled by next-generation sequencing of panels of genes involved in these disorders in order to establish as early as possible an accurate clinical and molecular diagnosis for a proper patient management.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2021-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/53/d5/tacg-14-279.PMC8180271.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39092446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-01eCollection Date: 2021-01-01DOI: 10.2147/TACG.S280066
Estephania Candelo, Maria Alejandra Estrada-Mesa, Adriana Jaramillo, Carlos Humberto Martinez-Cajas, Julio Cesar Osorio, Harry Pachajoa
Background: DiGeorge syndrome (DG) is a genetic disorder associated with 22q11 deletion. It involves various phenotypes, including craniofacial abnormalities, congenital heart disorders, endocrine dysfunction, cognitive deficits, and psychiatric disorders. Cases commonly involve multiple anomalies. However, little is known about the condition of the oral cavity in this disorder, although palate fissure, abnormal mandible, malocclusion, and tooth hypoplasia have been identified. We aimed to determine the odontological features of patients with 22q11.2 microdeletion, in relation to gingival health and oral hygiene. We report the systemic manifestations of nine patients and results of oral evaluation of two patients. In the oral examination, oral hygiene and gingivitis were evaluated.
Case presentation: In terms of the systemic manifestations, we found high frequencies of low weight and height at birth. In terms of the oral manifestations, both examined patients presented malocclusion, enamel hypoplasia, dental crowding, anodontia, and healthy periodontium.
Conclusion: Although DG has been documented to involve periodontium disease, the patients in this study exhibited more dental manifestations such as enamel defects, misalignment between the teeth and the two dental arches, anodontia, and dental crowding. As such, a multidisciplinary approach combining dentistry and healthcare is recommended in this case.
{"title":"The Oral Health of Patients with DiGeorge Syndrome (22q11) Microdeletion: A Case Report.","authors":"Estephania Candelo, Maria Alejandra Estrada-Mesa, Adriana Jaramillo, Carlos Humberto Martinez-Cajas, Julio Cesar Osorio, Harry Pachajoa","doi":"10.2147/TACG.S280066","DOIUrl":"https://doi.org/10.2147/TACG.S280066","url":null,"abstract":"<p><strong>Background: </strong>DiGeorge syndrome (DG) is a genetic disorder associated with 22q11 deletion. It involves various phenotypes, including craniofacial abnormalities, congenital heart disorders, endocrine dysfunction, cognitive deficits, and psychiatric disorders. Cases commonly involve multiple anomalies. However, little is known about the condition of the oral cavity in this disorder, although palate fissure, abnormal mandible, malocclusion, and tooth hypoplasia have been identified. We aimed to determine the odontological features of patients with 22q11.2 microdeletion, in relation to gingival health and oral hygiene. We report the systemic manifestations of nine patients and results of oral evaluation of two patients. In the oral examination, oral hygiene and gingivitis were evaluated.</p><p><strong>Case presentation: </strong>In terms of the systemic manifestations, we found high frequencies of low weight and height at birth. In terms of the oral manifestations, both examined patients presented malocclusion, enamel hypoplasia, dental crowding, anodontia, and healthy periodontium.</p><p><strong>Conclusion: </strong>Although DG has been documented to involve periodontium disease, the patients in this study exhibited more dental manifestations such as enamel defects, misalignment between the teeth and the two dental arches, anodontia, and dental crowding. As such, a multidisciplinary approach combining dentistry and healthcare is recommended in this case.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/b0/tacg-14-267.PMC8179788.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39092014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-20eCollection Date: 2021-01-01DOI: 10.2147/TACG.S261737
Bradley King, Jana McHugh, Katie Snape
BRCA2 is the most commonly implicated DNA damage repair gene associated with inherited prostate cancer. BRCA2 deficient prostate cancer typically presents at a younger age, is more poorly differentiated, and is associated with worse survival outcomes than non-BRCA2 associated prostate cancer. Despite these unfavourable prognostic implications, poly-ADP ribose polymerase inhibitors and platinum-based chemotherapy have been identified as potent targeted therapeutic agents towards BRCA1/2 deficient cancer cells. This review article explores the literature surrounding BRCA2-related prostate cancer through a familial clinical scenario. The investigation, diagnosis and management of BRCA2 deficient prostate cancer will be explored, alongside the implications of the identification of a germline pathogenic BRCA2 variant within a family, cascade screening and prostate cancer surveillance in unaffected male BRCA2 carriers. A greater understanding of the molecular pathogenesis of DNA damage repair gene deficient prostate cancer, coupled with new treatment paradigms and widened access to both somatic and germline genetic analysis for prostate cancer patients and their families will hopefully enable the robust implementation of high quality evidence-based clinical pathways for both the management and identification of BRCA2 deficient prostate cancer and improved screening, early detection and prevention strategies for individuals at increased genetic risk of prostate cancer.
{"title":"A Case-Based Clinical Approach to the Investigation, Management and Screening of Families with BRCA2 Related Prostate Cancer.","authors":"Bradley King, Jana McHugh, Katie Snape","doi":"10.2147/TACG.S261737","DOIUrl":"https://doi.org/10.2147/TACG.S261737","url":null,"abstract":"<p><p><i>BRCA2</i> is the most commonly implicated DNA damage repair gene associated with inherited prostate cancer. <i>BRCA2</i> deficient prostate cancer typically presents at a younger age, is more poorly differentiated, and is associated with worse survival outcomes than non-<i>BRCA2</i> associated prostate cancer. Despite these unfavourable prognostic implications, poly-ADP ribose polymerase inhibitors and platinum-based chemotherapy have been identified as potent targeted therapeutic agents towards <i>BRCA1/2</i> deficient cancer cells. This review article explores the literature surrounding <i>BRCA2</i>-related prostate cancer through a familial clinical scenario. The investigation, diagnosis and management of <i>BRCA2</i> deficient prostate cancer will be explored, alongside the implications of the identification of a germline pathogenic <i>BRCA2</i> variant within a family, cascade screening and prostate cancer surveillance in unaffected male <i>BRCA2</i> carriers. A greater understanding of the molecular pathogenesis of DNA damage repair gene deficient prostate cancer, coupled with new treatment paradigms and widened access to both somatic and germline genetic analysis for prostate cancer patients and their families will hopefully enable the robust implementation of high quality evidence-based clinical pathways for both the management and identification of <i>BRCA2</i> deficient prostate cancer and improved screening, early detection and prevention strategies for individuals at increased genetic risk of prostate cancer.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e9/f8/tacg-14-255.PMC8290889.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39210543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-29eCollection Date: 2021-01-01DOI: 10.2147/TACG.S262866
Hamza Hassan, Raphael Szalat
Multiple myeloma (MM) is a heterogeneous disease featured by clonal plasma cell proliferation and genomic instability. The advent of next-generation sequencing allowed unraveling the complex genomic landscape of the disease. Several recurrent genomic aberrations including immunoglobulin genes translocations, copy number abnormalities, complex chromosomal events, transcriptomic and epigenomic deregulation, and mutations define various molecular subgroups with distinct outcomes. In this review, we describe the recurrent genomic events identified in MM impacting patients' outcome and survival. These genomic aberrations constitute new markers that could be incorporated into a prognostication model to eventually guide therapy at every stage of the disease.
{"title":"Genetic Predictors of Mortality in Patients with Multiple Myeloma.","authors":"Hamza Hassan, Raphael Szalat","doi":"10.2147/TACG.S262866","DOIUrl":"https://doi.org/10.2147/TACG.S262866","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a heterogeneous disease featured by clonal plasma cell proliferation and genomic instability. The advent of next-generation sequencing allowed unraveling the complex genomic landscape of the disease. Several recurrent genomic aberrations including immunoglobulin genes translocations, copy number abnormalities, complex chromosomal events, transcriptomic and epigenomic deregulation, and mutations define various molecular subgroups with distinct outcomes. In this review, we describe the recurrent genomic events identified in MM impacting patients' outcome and survival. These genomic aberrations constitute new markers that could be incorporated into a prognostication model to eventually guide therapy at every stage of the disease.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2021-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6d/50/tacg-14-241.PMC8092627.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38952541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H syndrome is an extremely rare autosomal recessive affection caused by biallelic mutations in the SLC29A3 gene encoding the human equilibrative nucleoside transporter hENT3. The hallmark signs are cutaneous consisting of hyperpigmentation and hypertrichosis patches. Besides, associated systemic manifestations are highly various reflecting phenotypic pleiotropism. Herein, we report a first case of pseudo-Meigs' syndrome occurring in a young Tunisian H syndrome diagnosed patient with a novel homozygous frameshift mutation in exon 2 of the SLC29A3 gene: p.S15Pfs*86 inducing a premature stop codon. The patient developed ascites associated with left ovarian mass and she underwent surgery. After tumor resection, ascites disappeared rapidly. Histological examination showed serous cystadenoma of the ovary orienting the diagnosis towards pseudo-Meigs' syndrome.
{"title":"Pseudo-Meigs' Syndrome in Tunisian H Syndrome Female Patient: First Case Reported.","authors":"Yosra Zaimi, Myriam Ayari, Asma Mensi, Linda Bel Hadj Kacem, Leila Achouri, Meriem Bouzrara, Yosra Said, Leila Mouelhi, Radhouane Debbeche","doi":"10.2147/TACG.S306298","DOIUrl":"https://doi.org/10.2147/TACG.S306298","url":null,"abstract":"<p><p>H syndrome is an extremely rare autosomal recessive affection caused by biallelic mutations in the SLC29A3 gene encoding the human equilibrative nucleoside transporter hENT3. The hallmark signs are cutaneous consisting of hyperpigmentation and hypertrichosis patches. Besides, associated systemic manifestations are highly various reflecting phenotypic pleiotropism. Herein, we report a first case of pseudo-Meigs' syndrome occurring in a young Tunisian H syndrome diagnosed patient with a novel homozygous frameshift mutation in exon 2 of the SLC29A3 gene: p.S15Pfs*86 inducing a premature stop codon. The patient developed ascites associated with left ovarian mass and she underwent surgery. After tumor resection, ascites disappeared rapidly. Histological examination showed serous cystadenoma of the ovary orienting the diagnosis towards pseudo-Meigs' syndrome.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2021-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/67/37/tacg-14-235.PMC8055247.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38895841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-09eCollection Date: 2021-01-01DOI: 10.2147/TACG.S206076
Allisandra K Rha, Anne S Maguire, Douglas R Martin
The lysosomal storage disorder, GM1 gangliosidosis (GM1), is a neurodegenerative condition resulting from deficiency of the enzyme β-galactosidase (β-gal). Mutation of the GLB1 gene, which codes for β-gal, prevents cleavage of the terminal β-1,4-linked galactose residue from GM1 ganglioside. Subsequent accumulation of GM1 ganglioside and other substrates in the lysosome impairs cell physiology and precipitates dysfunction of the nervous system. Beyond palliative and supportive care, no FDA-approved treatments exist for GM1 patients. Researchers are critically evaluating the efficacy of substrate reduction therapy, pharmacological chaperones, enzyme replacement therapy, stem cell transplantation, and gene therapy for GM1. A Phase I/II clinical trial for GM1 children is ongoing to evaluate the safety and efficacy of adeno-associated virus-mediated GLB1 delivery by intravenous injection, providing patients and families with hope for the future.
{"title":"GM1 Gangliosidosis: Mechanisms and Management.","authors":"Allisandra K Rha, Anne S Maguire, Douglas R Martin","doi":"10.2147/TACG.S206076","DOIUrl":"10.2147/TACG.S206076","url":null,"abstract":"<p><p>The lysosomal storage disorder, GM1 gangliosidosis (GM1), is a neurodegenerative condition resulting from deficiency of the enzyme β-galactosidase (β-gal). Mutation of the <i>GLB1</i> gene, which codes for β-gal, prevents cleavage of the terminal β-1,4-linked galactose residue from GM1 ganglioside. Subsequent accumulation of GM1 ganglioside and other substrates in the lysosome impairs cell physiology and precipitates dysfunction of the nervous system. Beyond palliative and supportive care, no FDA-approved treatments exist for GM1 patients. Researchers are critically evaluating the efficacy of substrate reduction therapy, pharmacological chaperones, enzyme replacement therapy, stem cell transplantation, and gene therapy for GM1. A Phase I/II clinical trial for GM1 children is ongoing to evaluate the safety and efficacy of adeno-associated virus-mediated <i>GLB1</i> delivery by intravenous injection, providing patients and families with hope for the future.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2021-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e3/5a/tacg-14-209.PMC8044076.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38878068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}