Hacer Basan, E. Azak, I. Cetin, Esra Kılıç, Berrak Bilginer Gürbüz, Sümeyra Zeynep Özbey, Ç. Kasapkara
Introduction: Primary carnitine deficiency (PCD) is a rare autosomal recessive disorder caused by loss of function mutations in the solute carrier family 22 member 5 (SLC22A5) gene that encodes a high-affinity sodium-ion-dependent organic cation transporter protein (OCTN2). Carnitine deficiency can result in acute metabolic decompensation or, in a more insidious presentation, cardiomyopathy. Cardiomyopathy associated with PCD often presents with life-threatening heart failure. This presentation also usually includes skeletal muscle myopathy. Early recognition of this disorder and treatment with carnitine can avoid life-threatening complications related to cardiomyopathy. Case Presentation: Herein, we present a 10-month-old male patient with PCD, which was diagnosed while investigating the etiology of dilated cardiomyopathy and confirmed by molecular genetic analysis. Conclusion: Homozygous c.254_265 insGGCTCGCCACC (p.I89Gfs) pathogenic variant of the SLC22A5 gene was detected. With oral L-carnitine supplementation, the free carnitine level increased up to 14 μmol/L and the symptoms disappeared. LVEF increased by 45–70%. We would like to emphasize that this problem is a combination of the metabolic decompensation and the cardiac phenotypes, which are usually separated to either phenotype.
{"title":"A Rare Treatable Cause of Cardiomyopathy: Primary Carnitine Deficiency","authors":"Hacer Basan, E. Azak, I. Cetin, Esra Kılıç, Berrak Bilginer Gürbüz, Sümeyra Zeynep Özbey, Ç. Kasapkara","doi":"10.1159/000534932","DOIUrl":"https://doi.org/10.1159/000534932","url":null,"abstract":"Introduction: Primary carnitine deficiency (PCD) is a rare autosomal recessive disorder caused by loss of function mutations in the solute carrier family 22 member 5 (SLC22A5) gene that encodes a high-affinity sodium-ion-dependent organic cation transporter protein (OCTN2). Carnitine deficiency can result in acute metabolic decompensation or, in a more insidious presentation, cardiomyopathy. Cardiomyopathy associated with PCD often presents with life-threatening heart failure. This presentation also usually includes skeletal muscle myopathy. Early recognition of this disorder and treatment with carnitine can avoid life-threatening complications related to cardiomyopathy. Case Presentation: Herein, we present a 10-month-old male patient with PCD, which was diagnosed while investigating the etiology of dilated cardiomyopathy and confirmed by molecular genetic analysis. Conclusion: Homozygous c.254_265 insGGCTCGCCACC (p.I89Gfs) pathogenic variant of the SLC22A5 gene was detected. With oral L-carnitine supplementation, the free carnitine level increased up to 14 μmol/L and the symptoms disappeared. LVEF increased by 45–70%. We would like to emphasize that this problem is a combination of the metabolic decompensation and the cardiac phenotypes, which are usually separated to either phenotype.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"5 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139233276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pınar Özkan Kart, Yavuz Sahin, Nihal Yıldız, Alper Han Cebi, Gulnur Esenulku, Ali Cansu
Background: Perrault syndrome is an inherited disorder with clinical findings that differ according to sex. It is characterized by a variable age of onset and sensorineural hearing loss in both sexes, as well as ovarian dysfunction in females with a 46,XX karyotype. Although it is a rare autosomal recessive syndrome, with approximately 100 affected individuals reported in the literature, it shows both genotypic and phenotypic variations. Mutations in the HSD17B4 gene have been identified as one of the genetic causes of Perrault syndrome. Case Presentation: A female case and a male case from two different unrelated families with a new variant in the HSD17B4 gene, which were not previously described in the literature and were accompanied by hearing loss, skeletal anomalies, and neurological symptoms, were presented. Conclusion: We defined Perrault syndrome cases in Turkey caused by a novel mutation in HSD17B4. Whole-exome sequencing is a useful diagnostic technique with varying clinical results due to genetic and phenotypic heterogeneity.
{"title":"A Homozygous Missense Variant in <i>HSD17B4</i> Identified in Two Different Families","authors":"Pınar Özkan Kart, Yavuz Sahin, Nihal Yıldız, Alper Han Cebi, Gulnur Esenulku, Ali Cansu","doi":"10.1159/000534785","DOIUrl":"https://doi.org/10.1159/000534785","url":null,"abstract":"<b><i>Background:</i></b> Perrault syndrome is an inherited disorder with clinical findings that differ according to sex. It is characterized by a variable age of onset and sensorineural hearing loss in both sexes, as well as ovarian dysfunction in females with a 46,XX karyotype. Although it is a rare autosomal recessive syndrome, with approximately 100 affected individuals reported in the literature, it shows both genotypic and phenotypic variations. Mutations in the <i>HSD17B4</i> gene have been identified as one of the genetic causes of Perrault syndrome. <b><i>Case Presentation:</i></b> A female case and a male case from two different unrelated families with a new variant in the <i>HSD17B4</i> gene, which were not previously described in the literature and were accompanied by hearing loss, skeletal anomalies, and neurological symptoms, were presented. <b><i>Conclusion:</i></b> We defined Perrault syndrome cases in Turkey caused by a novel mutation in <i>HSD17B4</i>. Whole-exome sequencing is a useful diagnostic technique with varying clinical results due to genetic and phenotypic heterogeneity.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"10 7","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134956992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Murat Erdogan, Suleyman Sunkak, Oguzhan Bahadır, Muhammet Ensar Doğan, Yasin Ada, Burhan Balta
Introduction: Long QT syndrome (LQTS) is a common congenital cause of fatal cardiac arrhythmia. Characteristic clinical findings are prolonged QT interval and ventricular arrhythmia on electrocardiogram (ECG), syncope, seizure, and sudden death. It is a genetically heterogeneous disease. To date, disease-causing variant have been reported in seventeen genes. The AKAP9 is still considered controversial among those genes. Case Report: We report the case of a 10-year-old female who was born from a non-consanguineous Turkish couple. She visited pediatrics cardiology clinic presenting with dyspnea and tachycardia. Prolongation of the QT interval was detected in her ECG. Panel test associated with LQTS genes was performed. She was diagnosed with long QTS type 11 due to a heterozygous variant in AKAP9:c.11487_11489 delTACinsCGTA, p.(Thr3830ValfsTer12), that was revealed through next-generation sequencing test. The variant was also found in her mother and brother. Discussion and Conclusion: Novel heterozygous frameshift variant in the AKAP9 gene was considered as “Uncertain Significance (VUS)” in the ACMG classification. The novel variant is absent from population databases (PM2); it is a null variant (PVS1_moderate). AKAP9 gene has the lowest known rate among the causes of LQTS. Information is limited on genotype-phenotype correlation. Yet it is still among the candidate genes. Although the relationship of the AKAP9 gene with LQTS has not yet been fully indicated, individuals with a pathogenic variant in AKAP9 gene and silent carriers may be at risk for fatal cardiac events. Improvements of the genetic tests in the near future may contribute to the literature and clinical research about AKAP9 gene.
{"title":"A Novel Variant in <i>AKAP9</i> Gene, a Controversial Gene, in Long QT Syndrome","authors":"Murat Erdogan, Suleyman Sunkak, Oguzhan Bahadır, Muhammet Ensar Doğan, Yasin Ada, Burhan Balta","doi":"10.1159/000534624","DOIUrl":"https://doi.org/10.1159/000534624","url":null,"abstract":"<b><i>Introduction:</i></b> Long QT syndrome (LQTS) is a common congenital cause of fatal cardiac arrhythmia. Characteristic clinical findings are prolonged QT interval and ventricular arrhythmia on electrocardiogram (ECG), syncope, seizure, and sudden death. It is a genetically heterogeneous disease. To date, disease-causing variant have been reported in seventeen genes. The <i>AKAP9</i> is still considered controversial among those genes. <b><i>Case Report:</i></b> We report the case of a 10-year-old female who was born from a non-consanguineous Turkish couple. She visited pediatrics cardiology clinic presenting with dyspnea and tachycardia. Prolongation of the QT interval was detected in her ECG. Panel test associated with LQTS genes was performed. She was diagnosed with long QTS type 11 due to a heterozygous variant in <i>AKAP9:</i>c.11487_11489 delTACinsCGTA, p.(Thr3830ValfsTer12), that was revealed through next-generation sequencing test. The variant was also found in her mother and brother. <b><i>Discussion and Conclusion:</i></b> Novel heterozygous frameshift variant in the <i>AKAP9</i> gene was considered as “Uncertain Significance (VUS)” in the ACMG classification. The novel variant is absent from population databases (PM2); it is a null variant (PVS1_moderate). <i>AKAP9</i> gene has the lowest known rate among the causes of LQTS. Information is limited on genotype-phenotype correlation. Yet it is still among the candidate genes. Although the relationship of the <i>AKAP9</i> gene with LQTS has not yet been fully indicated, individuals with a pathogenic variant in AKAP9 gene and silent carriers may be at risk for fatal cardiac events. Improvements of the genetic tests in the near future may contribute to the literature and clinical research about <i>AKAP9</i> gene.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"54 18","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136282223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aysenur Engin Erdal, Oya Kıreker Köylü, Ahmet Cevdet Ceylan, Çiğdem Seher Kasapkara, Ebru Tunçez, Meral Topçu
Introduction: Sepiapterin reductase deficiency (SRD) is an exceedingly rare neurotransmitter disease caused by an enzyme error involved in the synthesis of tetrahydrobiopterin (BH4). It has been described in nearly 60 cases so far. The clinical manifestations include motor and speech delay, axial hypotonia, dystonia, weakness, oculogyric crises, diurnal fluctuation, and improvement of symptoms during sleep. Molecular genetic analysis can demonstrate pathogenic mutations in the SPR gene, allowing for a definitive diagnosis. Levodopa/carbidopa and 5-hydroxytryptophan are used for treatment. Case Presentation: We present a 19-year-old male patient who was evaluated for dysarthria, axial hypotonia, limb dystonia, and movement disorder. The parents described the current patient’s history with febrile seizures since 9 months of age, as well as speech and neuromotor developmental retardation, which indicated that the disease began in infancy. The basal metabolic work-up was normal except for hyperprolactinemia. The definitive diagnosis of SRD was confirmed by whole exome sequencing (WES) analysis, which revealed a homozygous pathogenic mutation c.655C>T (p.Arg219*) (rs779204655) in the SPR gene. After treatment, we noted significant improvements in dystonia, axial hypotonia, and dysarthria. Conclusion: WES analysis offers a more expeditious and dependable method for diagnosing difficult cases exhibiting neurodevelopmental problems and thus renders the possibilities of early management.
{"title":"Sepiapterin Reductase Deficiency Misdiagnosed as Neurological Sequelae of Meningitis","authors":"Aysenur Engin Erdal, Oya Kıreker Köylü, Ahmet Cevdet Ceylan, Çiğdem Seher Kasapkara, Ebru Tunçez, Meral Topçu","doi":"10.1159/000534587","DOIUrl":"https://doi.org/10.1159/000534587","url":null,"abstract":"<b><i>Introduction:</i></b> Sepiapterin reductase deficiency (SRD) is an exceedingly rare neurotransmitter disease caused by an enzyme error involved in the synthesis of tetrahydrobiopterin (BH4). It has been described in nearly 60 cases so far. The clinical manifestations include motor and speech delay, axial hypotonia, dystonia, weakness, oculogyric crises, diurnal fluctuation, and improvement of symptoms during sleep. Molecular genetic analysis can demonstrate pathogenic mutations in the <i>SPR</i> gene, allowing for a definitive diagnosis. Levodopa/carbidopa and 5-hydroxytryptophan are used for treatment. <b><i>Case Presentation:</i></b> We present a 19-year-old male patient who was evaluated for dysarthria, axial hypotonia, limb dystonia, and movement disorder. The parents described the current patient’s history with febrile seizures since 9 months of age, as well as speech and neuromotor developmental retardation, which indicated that the disease began in infancy. The basal metabolic work-up was normal except for hyperprolactinemia. The definitive diagnosis of SRD was confirmed by whole exome sequencing (WES) analysis, which revealed a homozygous pathogenic mutation c.655C&gt;T (p.Arg219*) (rs779204655) in the <i>SPR</i> gene. After treatment, we noted significant improvements in dystonia, axial hypotonia, and dysarthria. <b><i>Conclusion:</i></b> WES analysis offers a more expeditious and dependable method for diagnosing difficult cases exhibiting neurodevelopmental problems and thus renders the possibilities of early management.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" 27","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135340675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vehap Topcu, Said Furkan Yildirim, Husnu Mutlu Turan
Introduction: Ciliopathies with major skeletal involvement embrace a group of heterogeneous disorders caused by pathogenic variants in a group of diverse genes. A narrow thorax with shortening of long bones inspires a clinical entity underlined by dysfunction of primary cilia. Currently, more than 23 genes are listed in the OMIM database corresponding to this clinical entity: WDR19/34/35/60, IFT43/52/80/81/140/172, DYNC2LI1, TTC21B, DYNLT2B, EVC2, EVC, INTU, NEK1, CEP120, DYNC2H1, KIAA0586, SRTD1, KIAA0753, and SRTD12. Recently, individuals with biallelic loss-of-function variants in GRK2 are shown to demonstrate a phenotype compatible with Jeune syndrome. Experimental evidence has shown that impaired function of GRK2 compromises cilia-based signaling of Hedgehog pathway as well as Wnt signaling, while cilia morphology remains intact. Hence, GRK2 is now considered an essential protein in regulation of the skeletogenesis. Case Presentation: We presented a female infant born to a consanguineous marriage who was found to have a biallelic p.R474* alteration in GRK2 in reanalysis of the whole-exome sequencing (WES) data. The patient was exhibiting major clinical features of Jeune syndrome, such as shortened long bones, ribs, and narrow thorax. Discussion: Our reanalysis of WES data revealed a likely pathogenic biallelic variant in the GRK2 which is probably responsible for the Jeune syndrome phenotype in the patient. Hence, our report supports the recently discovered association of GRK2 loss-of-function variants with Jeune syndrome phenotype and emphasizes the significance of reanalysis of WES data, notably in patients with phenotypes suggestive of a such discernible Mendelian disorder.
{"title":"Reanalysis of Whole-Exome Sequencing Data of an Infant with Suspected Diagnosis of Jeune Syndrome Revealed a Likely Pathogenic Variant in <i>GRK2:</i> A Newly Associated Gene for Jeune Syndrome Phenotype","authors":"Vehap Topcu, Said Furkan Yildirim, Husnu Mutlu Turan","doi":"10.1159/000534031","DOIUrl":"https://doi.org/10.1159/000534031","url":null,"abstract":"<b><i>Introduction:</i></b> Ciliopathies with major skeletal involvement embrace a group of heterogeneous disorders caused by pathogenic variants in a group of diverse genes. A narrow thorax with shortening of long bones inspires a clinical entity underlined by dysfunction of primary cilia. Currently, more than 23 genes are listed in the OMIM database corresponding to this clinical entity: WDR19/34/35/60, IFT43/52/80/81/140/172, DYNC2LI1, TTC21B, DYNLT2B, EVC2, EVC, INTU, NEK1, CEP120, DYNC2H1, KIAA0586, SRTD1, KIAA0753, and SRTD12. Recently, individuals with biallelic loss-of-function variants in <i>GRK2</i> are shown to demonstrate a phenotype compatible with Jeune syndrome. Experimental evidence has shown that impaired function of <i>GRK2</i> compromises cilia-based signaling of Hedgehog pathway as well as Wnt signaling, while cilia morphology remains intact. Hence, <i>GRK2</i> is now considered an essential protein in regulation of the skeletogenesis. <b><i>Case Presentation:</i></b> We presented a female infant born to a consanguineous marriage who was found to have a biallelic p.R474* alteration in <i>GRK2</i> in reanalysis of the whole-exome sequencing (WES) data. The patient was exhibiting major clinical features of Jeune syndrome, such as shortened long bones, ribs, and narrow thorax. <b><i>Discussion:</i></b> Our reanalysis of WES data revealed a likely pathogenic biallelic variant in the <i>GRK2</i> which is probably responsible for the Jeune syndrome phenotype in the patient. Hence, our report supports the recently discovered association of <i>GRK2</i> loss-of-function variants with Jeune syndrome phenotype and emphasizes the significance of reanalysis of WES data, notably in patients with phenotypes suggestive of a such discernible Mendelian disorder.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"79 5‐6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135818268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhour El Amrani, Abdelhafid Natiq, Aziza Sbiti, Ilham Ratbi, Thomas Liehr, Abdelaziz Sefiani, Maryem Sahli
Introduction: Currarino syndrome is a rare syndrome with multiple congenital anomalies including sacral agenesis, anorectal malformation, and presence of a presacral mass. Currarino syndrome is considered to be an autosomal dominant inherited disorder, with low penetrance and variable expressivity, but sporadic cases have also been reported. Mutations in MNX1 gene, mapped to 7q36, are the main causes of this syndrome. To the best of our knowledge, less than 400 cases of this syndrome have been mentioned in the literature. Currarino syndrome is often seen in children and considered to be rare in adults; it is mostly found as incidental finding and suspected to be underdiagnosed. Case Presentation: Recognizing the rarity of this syndrome, we present here two siblings with incomplete form of Currarino syndrome combined with microcephaly and intellectual disability. Banding and molecular cytogenetics were used to characterize the origin of this disorder. Banding cytogenetics together with molecular cytogenetics revealed an unbalanced translocation t(7;21)(q36.2;p11.3)mat, leading to a deletion of the 7q36 region in both affected children. Conclusion: This report highlights the importance of cytogenetics in diagnosis of rare genetic syndromes, with impact on genetic counseling of patients and their families. To the best of our knowledge, this is the first Moroccan Currarino syndrome case due to an unbalanced translocation leading to a der(7)t(7;21)(q36.2;p11.3). Also, this is the first Currarino syndrome case associated with a deletion in 7q36 to be reported in Morocco.
{"title":"Currarino Syndrome in Two Moroccan Siblings with Inherited 7q36 Deletion due to Maternal t(7;21)(q36;p11)mat: A Case Report","authors":"Zhour El Amrani, Abdelhafid Natiq, Aziza Sbiti, Ilham Ratbi, Thomas Liehr, Abdelaziz Sefiani, Maryem Sahli","doi":"10.1159/000534432","DOIUrl":"https://doi.org/10.1159/000534432","url":null,"abstract":"<b><i>Introduction:</i></b> Currarino syndrome is a rare syndrome with multiple congenital anomalies including sacral agenesis, anorectal malformation, and presence of a presacral mass. Currarino syndrome is considered to be an autosomal dominant inherited disorder, with low penetrance and variable expressivity, but sporadic cases have also been reported. Mutations in <i>MNX1</i> gene, mapped to 7q36, are the main causes of this syndrome. To the best of our knowledge, less than 400 cases of this syndrome have been mentioned in the literature. Currarino syndrome is often seen in children and considered to be rare in adults; it is mostly found as incidental finding and suspected to be underdiagnosed. <b><i>Case Presentation:</i></b> Recognizing the rarity of this syndrome, we present here two siblings with incomplete form of Currarino syndrome combined with microcephaly and intellectual disability. Banding and molecular cytogenetics were used to characterize the origin of this disorder. Banding cytogenetics together with molecular cytogenetics revealed an unbalanced translocation t(7;21)(q36.2;p11.3)mat, leading to a deletion of the 7q36 region in both affected children. <b><i>Conclusion:</i></b> This report highlights the importance of cytogenetics in diagnosis of rare genetic syndromes, with impact on genetic counseling of patients and their families. To the best of our knowledge, this is the first Moroccan Currarino syndrome case due to an unbalanced translocation leading to a der(7)t(7;21)(q36.2;p11.3). Also, this is the first Currarino syndrome case associated with a deletion in 7q36 to be reported in Morocco.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"80 4‐6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135818265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cansu Kethuda Ensert Cihan, Halil Tuna Akar, Yılmaz Yıldız, Merve Sogukpinar, Gulen Eda Utine, Hasan Tolga Çelik
Introduction: Propionic acidemia (PA) is an inborn error of organic acid metabolism inherited in an autosomal recessive manner. The neonatal-onset disease may present with feeding difficulties and vomiting; seizures, coma, and death may occur if untreated. In addition, catabolic processes such as infections and surgical procedures could cause metabolic decompensation, so patients with organic acidemia should be followed closely. Case Presentation: Here, a patient diagnosed with PA and Apert syndrome in the neonatal period and the complications caused by the coexistence of the two entities are mentioned. The difficulties precipitated by the coexistence of Apert syndrome and PA make this case unique. She has had prolonged hospitalizations due to metabolic decompensations after cranioplasty and inguinal hernia repair, both triggered by nosocomial respiratory infections, complicating both the surgical treatment of Apert syndrome and the management of PA. Conclusion: Coexistence of these two serious disorders mandates a more prudent clinical management as Apert syndrome patients undergo several surgical procedures, rendering them susceptible to catabolic decompensations.
{"title":"Coexistence of Two Rare Conditions Complicating the Other’s Management: Propionic Acidemia and Apert Syndrome","authors":"Cansu Kethuda Ensert Cihan, Halil Tuna Akar, Yılmaz Yıldız, Merve Sogukpinar, Gulen Eda Utine, Hasan Tolga Çelik","doi":"10.1159/000534380","DOIUrl":"https://doi.org/10.1159/000534380","url":null,"abstract":"<b><i>Introduction:</i></b> Propionic acidemia (PA) is an inborn error of organic acid metabolism inherited in an autosomal recessive manner. The neonatal-onset disease may present with feeding difficulties and vomiting; seizures, coma, and death may occur if untreated. In addition, catabolic processes such as infections and surgical procedures could cause metabolic decompensation, so patients with organic acidemia should be followed closely. <b><i>Case Presentation:</i></b> Here, a patient diagnosed with PA and Apert syndrome in the neonatal period and the complications caused by the coexistence of the two entities are mentioned. The difficulties precipitated by the coexistence of Apert syndrome and PA make this case unique. She has had prolonged hospitalizations due to metabolic decompensations after cranioplasty and inguinal hernia repair, both triggered by nosocomial respiratory infections, complicating both the surgical treatment of Apert syndrome and the management of PA. <b><i>Conclusion:</i></b> Coexistence of these two serious disorders mandates a more prudent clinical management as Apert syndrome patients undergo several surgical procedures, rendering them susceptible to catabolic decompensations.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"43 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136234095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of familial cerebral small vessel disease in adults and is caused by NOTCH3 variants. Clinical manifestations of CADASIL include recurrent ischemic strokes, dementia, migraine or migraineous headaches, epileptic seizures, and psychiatric disorders. The clinical-radiological phenotype of the disease is also highly variable. In this study, we investigated the variability of clinical, radiological, and genetic data in patients analyzed for NOTCH3 variant in our clinic. Methods: We performed clinical and neuropsychological examination, cerebral magnetic resonance imaging (MRI) and Doppler sonography of cerebral arteries in all patients. Next-generation sequencing test was used for detect variants in NOTCH3 gene from all CADASIL patients. Results: By using the next-generation sequencing method, heterozygous c.380C>T pathogenic variant was detected in the 4th exon of the NOTCH3 gene in 3 patients. This is a previously unreported novel variant and resulted in the replacement of the amino acid Proline at 127th position with Leucine. Discussion and Conclusion: The discovery of this novel pathogenic variant region may contribute to the expansion of the clinical and genetic spectrum of diseases associated with NOTCH3, leading to further research and treatment options for this disease in the future.
{"title":"Detecting a Novel <i>NOTCH3</i> Variant in Patients with Suspected CADASIL: A Single Center Study","authors":"Zeynep Selcan Şanli, Özlem Anlaş","doi":"10.1159/000534243","DOIUrl":"https://doi.org/10.1159/000534243","url":null,"abstract":"<b><i>Introduction:</i></b> Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of familial cerebral small vessel disease in adults and is caused by <i>NOTCH3</i> variants. Clinical manifestations of CADASIL include recurrent ischemic strokes, dementia, migraine or migraineous headaches, epileptic seizures, and psychiatric disorders. The clinical-radiological phenotype of the disease is also highly variable. In this study, we investigated the variability of clinical, radiological, and genetic data in patients analyzed for <i>NOTCH3</i> variant in our clinic. <b><i>Methods:</i></b> We performed clinical and neuropsychological examination, cerebral magnetic resonance imaging (MRI) and Doppler sonography of cerebral arteries in all patients. Next-generation sequencing test was used for detect variants in <i>NOTCH3</i> gene from all CADASIL patients. <b><i>Results:</i></b> By using the next-generation sequencing method, heterozygous c.380C&gt;T pathogenic variant was detected in the 4th exon of the <i>NOTCH3</i> gene in 3 patients. This is a previously unreported novel variant and resulted in the replacement of the amino acid Proline at 127th position with Leucine. <b><i>Discussion and Conclusion:</i></b> The discovery of this novel pathogenic variant region may contribute to the expansion of the clinical and genetic spectrum of diseases associated with NOTCH3, leading to further research and treatment options for this disease in the future.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"25 11","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135567337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Limb-girdle muscular dystrophies (LGMDs) are clinically and genetically heterogeneous muscle disorders. We aimed to share the diagnostic yield of an NGS gene panel containing LGMD-related genes and our experience with LGMD. Methods: Between February 2019 and October 2022, patients with a suspicion of LGMD and their relatives were reviewed in terms of demographic, clinical, and individual genetic data, age of symptom onset, sex, clinical features, LGMD types, cardiac involvement, muscle biopsy results, family history, and consanguinity. Our NGS gene panel consisted of ANO5, CAPN3, CAV3, DAG1, DES, DNAJB6, DYSF, FKTN, FLNC, FRKP, GAA, GMPPB, HNRNPDL, ISPD, LIMS2, LMNA, MYOT, PLEC, POMGNT1, POMK, POMT1, POMT2, SGCA, SGCB, SGCD, SGCG, TCAP, TNPO3, TRAPPC11, TRIM32, and TTN genes. Results: The diagnosis rate was 61.1% (11/18). Twelve (80%) patients with LGMD were male and three (20%) were female. The median age was 15.9 (range, 1.5–39) years. Our patient collective was drawn up out of patients with the following variants: LGMDR1 (n = 6; 40%), LGMDR2 (n = 4; 26.6%), LGMDR3 (n = 4; 26.6%), and LGMDR12 (n = 1; 6.7%). Conclusion: The present study showed that the NGS panel has a high success rate in the diagnosis of LGMD and contributes to early diagnosis.
{"title":"Molecular Diagnosis of Limb-Girdle Muscular Dystrophy Using Next-Generation Sequencing Panels","authors":"Gamze Sarıkaya Uzan, Ceren Yılmaz Uzman, Tayfun Çinleti, Çağatay Günay, Ayfer Ülgenalp, Semra Hiz Kurul, Uluç Yiş","doi":"10.1159/000533976","DOIUrl":"https://doi.org/10.1159/000533976","url":null,"abstract":"<b><i>Introduction:</i></b> Limb-girdle muscular dystrophies (LGMDs) are clinically and genetically heterogeneous muscle disorders. We aimed to share the diagnostic yield of an NGS gene panel containing LGMD-related genes and our experience with LGMD. <b><i>Methods:</i></b> Between February 2019 and October 2022, patients with a suspicion of LGMD and their relatives were reviewed in terms of demographic, clinical, and individual genetic data, age of symptom onset, sex, clinical features, LGMD types, cardiac involvement, muscle biopsy results, family history, and consanguinity. Our NGS gene panel consisted of <i>ANO5, CAPN3, CAV3, DAG1, DES, DNAJB6, DYSF, FKTN, FLNC, FRKP, GAA, GMPPB, HNRNPDL, ISPD, LIMS2, LMNA, MYOT, PLEC, POMGNT1, POMK, POMT1, POMT2, SGCA, SGCB, SGCD, SGCG, TCAP, TNPO3, TRAPPC11, TRIM32,</i> and <i>TTN</i> genes. <b><i>Results:</i></b> The diagnosis rate was 61.1% (11/18). Twelve (80%) patients with LGMD were male and three (20%) were female. The median age was 15.9 (range, 1.5–39) years. Our patient collective was drawn up out of patients with the following variants: LGMDR1 (<i>n</i> = 6; 40%), LGMDR2 (<i>n</i> = 4; 26.6%), LGMDR3 (<i>n</i> = 4; 26.6%), and LGMDR12 (<i>n</i> = 1; 6.7%). <b><i>Conclusion:</i></b> The present study showed that the NGS panel has a high success rate in the diagnosis of LGMD and contributes to early diagnosis.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136078830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nahid Vafaei, Ali Mohebbi, Zahra Rezaei, Morteza Heidari, Sareh Hosseinpour, Ali Zare Dehnavi, Azin Ghamari, Masoud Salehipour, Ali Rabbani, Nejat Mahdieh, Mahmoud Reza Ashrafi
Introduction:TPP1 variants have been identified as a causative agent of neuronal ceroid lipofuscinosis 2 disease, that ataxia is one of its clinical features. Therefore, here, molecular study of TPP1 variants is presented in an Iranian cohort and a novel pathogenic variant is described. Methods: This investigation was conducted as a cross-sectional study in a tertiary referral hospital, Children’s Medical Center, Pediatrics Center of Excellence. Clinical presentations and pedigrees were documented. Patients with cerebellar ataxia were enrolled in this study. Next-generation sequencing was applied to confirm the diagnosis. Segregation and bioinformatics analyses were also done for the variants using Sanger sequencing. Results: Forty-five patients were included in our study. The mean age of onset was 104 (+55.60) months (minimum = 31 months, maximum = 216 months). The majority of cases (73.3%) were born to consanguineous parents and only 1 patient (2.2%) had an affected sibling. Of the 45 patients, only 1 patient with a novel pathogenic variant (c.1425_1425+1delinsAT, p.A476Cfs*15) in the TPP1 gene was identified. Discussion: The main strength of current study is the relatively large sample size. Besides, a novel pathogenic variant could be important toward the diagnosis and management of this condition. With significant advances in various therapies, early diagnosis could improve the treatments using personalized-based medicine.
{"title":"<i>TPP1</i> Variants in Iranian patients: A Novel Pathogenic Homozygous Variant Causing Neuronal Ceroid Lipofuscinosis 2","authors":"Nahid Vafaei, Ali Mohebbi, Zahra Rezaei, Morteza Heidari, Sareh Hosseinpour, Ali Zare Dehnavi, Azin Ghamari, Masoud Salehipour, Ali Rabbani, Nejat Mahdieh, Mahmoud Reza Ashrafi","doi":"10.1159/000534100","DOIUrl":"https://doi.org/10.1159/000534100","url":null,"abstract":"<b><i>Introduction:</i></b> <i>TPP1</i> variants have been identified as a causative agent of neuronal ceroid lipofuscinosis 2 disease, that ataxia is one of its clinical features. Therefore, here, molecular study of <i>TPP1</i> variants is presented in an Iranian cohort and a novel pathogenic variant is described. <b><i>Methods:</i></b> This investigation was conducted as a cross-sectional study in a tertiary referral hospital, Children’s Medical Center, Pediatrics Center of Excellence. Clinical presentations and pedigrees were documented. Patients with cerebellar ataxia were enrolled in this study. Next-generation sequencing was applied to confirm the diagnosis. Segregation and bioinformatics analyses were also done for the variants using Sanger sequencing. <b><i>Results:</i></b> Forty-five patients were included in our study. The mean age of onset was 104 (+55.60) months (minimum = 31 months, maximum = 216 months). The majority of cases (73.3%) were born to consanguineous parents and only 1 patient (2.2%) had an affected sibling. Of the 45 patients, only 1 patient with a novel pathogenic variant (c.1425_1425+1delinsAT, p.A476Cfs*15) in the <i>TPP1</i> gene was identified. <b><i>Discussion:</i></b> The main strength of current study is the relatively large sample size. Besides, a novel pathogenic variant could be important toward the diagnosis and management of this condition. With significant advances in various therapies, early diagnosis could improve the treatments using personalized-based medicine.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136078657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：