Pub Date : 2016-02-01Epub Date: 2016-01-30DOI: 10.4172/2157-7412.1000284
Isha Dey, Kalpit Shah, Neil A Bradbury
The recent FDA approval of two drugs to treat the basic defect in cystic fibrosis has given hope to patients and their families battling this devastating disease. Over many years, with heavy financial investment from Vertex Pharmaceuticals and the Cystic Fibrosis Foundation, pre-clinical evaluation of thousands of synthetic drugs resulted in the production of Kalydeco and Orkambi. Yet, despite the success of this endeavor, many other compounds have been proposed as therapeutic agents in the treatment of CF. Of note, several of these compounds are naturally occurring, and are present in spices from the grocery store and over the counter preparations in health food stores. In this short review, we look at three such compounds, genistein, curcumin, and resveratrol, and evaluate the scientific support for their use as therapeutic agents in the treatment of patients with CF.
{"title":"Natural Compounds as Therapeutic Agents in the Treatment Cystic Fibrosis.","authors":"Isha Dey, Kalpit Shah, Neil A Bradbury","doi":"10.4172/2157-7412.1000284","DOIUrl":"https://doi.org/10.4172/2157-7412.1000284","url":null,"abstract":"<p><p>The recent FDA approval of two drugs to treat the basic defect in cystic fibrosis has given hope to patients and their families battling this devastating disease. Over many years, with heavy financial investment from Vertex Pharmaceuticals and the Cystic Fibrosis Foundation, pre-clinical evaluation of thousands of synthetic drugs resulted in the production of Kalydeco and Orkambi. Yet, despite the success of this endeavor, many other compounds have been proposed as therapeutic agents in the treatment of CF. Of note, several of these compounds are naturally occurring, and are present in spices from the grocery store and over the counter preparations in health food stores. In this short review, we look at three such compounds, genistein, curcumin, and resveratrol, and evaluate the scientific support for their use as therapeutic agents in the treatment of patients with CF.</p>","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2157-7412.1000284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34406308","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 : 2016-02-01DOI: 10.4172/2157-7412.1000I101
E. Abdalla, K. Nabil, G. Elhady
{"title":"Its not Mccune-Albright Syndrome, Its Neurofibromatosis-1","authors":"E. Abdalla, K. Nabil, G. Elhady","doi":"10.4172/2157-7412.1000I101","DOIUrl":"https://doi.org/10.4172/2157-7412.1000I101","url":null,"abstract":"","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88257021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-09DOI: 10.4172/2157-7412.1000282
P. Chang, R. Fisch
PKU mothers have a high incidence of spontaneous abortion. The consequences of untreated pregnancies are severely detrimental to their offspring. It manifested by intrauterine growth retardation with microcephaly, congenital malformations and abnormal intellectual development. Infants’ pathology is independent of fetal genotype, but is directly correlated with excessive phenylalaninaemia of the mother throughout pregnancy. PKU mothers can produce healthy infant if they maintain a very restricted and controlled diet prior conception and during pregnancy. However to maintain a well-controlled diet prior to conception and during pregnancy is not possible in most cases, and significant mental and/or physical disability can result in children born due to either the delay or the not well controlled dietary treatment. We, previously, described the first child born using, non-PKU, gestational carrier with a PKU mother’s egg and the husband’s sperm. In this report, we present the normal developmental outcome of this infant at 4years 7 month of age. We suggest that doctors who take care of PKU females could suggest gestational carriers as an alternative therapy for MPKU.
{"title":"Normal Child by a Gestational Carrier of a Phenylketonuria (PKU) Mother-An Alternative to Diet","authors":"P. Chang, R. Fisch","doi":"10.4172/2157-7412.1000282","DOIUrl":"https://doi.org/10.4172/2157-7412.1000282","url":null,"abstract":"PKU mothers have a high incidence of spontaneous abortion. The consequences of untreated pregnancies are severely detrimental to their offspring. It manifested by intrauterine growth retardation with microcephaly, congenital malformations and abnormal intellectual development. Infants’ pathology is independent of fetal genotype, but is directly correlated with excessive phenylalaninaemia of the mother throughout pregnancy. PKU mothers can produce healthy infant if they maintain a very restricted and controlled diet prior conception and during pregnancy. However to maintain a well-controlled diet prior to conception and during pregnancy is not possible in most cases, and significant mental and/or physical disability can result in children born due to either the delay or the not well controlled dietary treatment. We, previously, described the first child born using, non-PKU, gestational carrier with a PKU mother’s egg and the husband’s sperm. In this report, we present the normal developmental outcome of this infant at 4years 7 month of age. We suggest that doctors who take care of PKU females could suggest gestational carriers as an alternative therapy for MPKU.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"11 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2016-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81046960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-06DOI: 10.4172/2157-7412.1000283
S. Jaiswal, Aishvarya Upadhyay, Akhtar Ali, S. Upadhyay, Ashok Kumar, Anil Rai
Two familial cases of Robertsonian translocation 13;14 [rob t(13;14)] and its clinical manifestation in children are discussed in present report. In case-1, father and child both were having [rob t(13;14)] with karyotype [45,XYrob(13;14)(q10;q10)] and [46,XY,rob(13;14)(q10;q10),+21] respectively. The child was presented with clinical characteristics of Down syndrome (DS) due to trisomy 21. The child and father both were having soft sub-mucous cleft palate. In case-2, child and mother both were having rob t(13;14) with karyotype [45,XX,rob(13;14)(q10;q10)]. Mother was phenotypically normal but both of her children were presented with gross developmental delay for all the four areas, i.e., gross motor, adaptive, language and personal social behavior. Interestingly all the carriers of [rob t(13;14)] showed abnormal clinical features: like soft sub-mucous cleft palate with DS in case-1 child, soft sub-mucous cleft palate and Inter Chromosomal Effect (ICE) in case-1 father, miscarriage and birth of children with congenital problem in case-2 mother and gross developmental delay in case-2 child. It was assumed that the co-occurrence of [rob t(13;14)] and trisomy 21 in case-1 child was due to phenomenon of ICE in father carrying [45,XY,rob(13;14)(q10;q10)].
{"title":"Two Familial Cases of Robertsonian Transloacations 13; 14 and Its Clinical Consequences","authors":"S. Jaiswal, Aishvarya Upadhyay, Akhtar Ali, S. Upadhyay, Ashok Kumar, Anil Rai","doi":"10.4172/2157-7412.1000283","DOIUrl":"https://doi.org/10.4172/2157-7412.1000283","url":null,"abstract":"Two familial cases of Robertsonian translocation 13;14 [rob t(13;14)] and its clinical manifestation in children are discussed in present report. In case-1, father and child both were having [rob t(13;14)] with karyotype [45,XYrob(13;14)(q10;q10)] and [46,XY,rob(13;14)(q10;q10),+21] respectively. The child was presented with clinical characteristics of Down syndrome (DS) due to trisomy 21. The child and father both were having soft sub-mucous cleft palate. In case-2, child and mother both were having rob t(13;14) with karyotype [45,XX,rob(13;14)(q10;q10)]. Mother was phenotypically normal but both of her children were presented with gross developmental delay for all the four areas, i.e., gross motor, adaptive, language and personal social behavior. Interestingly all the carriers of [rob t(13;14)] showed abnormal clinical features: like soft sub-mucous cleft palate with DS in case-1 child, soft sub-mucous cleft palate and Inter Chromosomal Effect (ICE) in case-1 father, miscarriage and birth of children with congenital problem in case-2 mother and gross developmental delay in case-2 child. It was assumed that the co-occurrence of [rob t(13;14)] and trisomy 21 in case-1 child was due to phenomenon of ICE in father carrying [45,XY,rob(13;14)(q10;q10)].","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"67 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2016-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88476775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-02DOI: 10.4172/2157-7412.1000278
M. Salvatore, A. Magrelli, Valentini Flamini, A. Brunati, E. Basso, R. Romagnoli, E. David, D. Taruscio
Hepatoblastoma (HB) is the most common liver cancer in infants younger than 3 years. Its onset has been associated with other genetic syndromes and some genetic and biochemical markers has been identified recently in this neoplasia. Nevertheless the patients have a poor prognosis and the resection or transplantation remains the only effective therapeutic approach. The identification of non-invasive markers may represent an innovative approach and may contribute to a more accurate histological classification of this tumor. We previously demonstrated that some microRNAs are helpful in discriminating HB from hepatocellular carcinoma. In this study, we describe the involvement of the two forms of microRNA-483 (-3p and -5p) in a selected cohort of HB patients who underwent surgical resection or liver transplantation. Differently from other liver diseases we observed that the quantitative expression of the two forms did not significantly changed among patients. Furthermore, 3p/5p ratio was different between HB and non-HB samples, being positive in the latter and negative in HB samples. Influence of concomitant treatments in the expression of miR-483 (i.e. chemotherapy, and immunosuppressive drugs) was also evaluated and no changes were found in the follow-up. In conclusion the expression and function of miR-483-3p/5p in HB still remains unclear and further studies are needed to elucidate the possible mechanisms that regulate the different strand selection between the two forms of microRNA-483 in patients affected by HB. We deem that the analysis of microRNA-483 different forms could be useful for the molecular identification of HB patients and the discrimination with non-HB patient.
{"title":"Hepatoblastoma and microRNA-483 Two Forms and One Outcome","authors":"M. Salvatore, A. Magrelli, Valentini Flamini, A. Brunati, E. Basso, R. Romagnoli, E. David, D. Taruscio","doi":"10.4172/2157-7412.1000278","DOIUrl":"https://doi.org/10.4172/2157-7412.1000278","url":null,"abstract":"Hepatoblastoma (HB) is the most common liver cancer in infants younger than 3 years. Its onset has been associated with other genetic syndromes and some genetic and biochemical markers has been identified recently in this neoplasia. Nevertheless the patients have a poor prognosis and the resection or transplantation remains the only effective therapeutic approach. The identification of non-invasive markers may represent an innovative approach and may contribute to a more accurate histological classification of this tumor. We previously demonstrated that some microRNAs are helpful in discriminating HB from hepatocellular carcinoma. In this study, we describe the involvement of the two forms of microRNA-483 (-3p and -5p) in a selected cohort of HB patients who underwent surgical resection or liver transplantation. Differently from other liver diseases we observed that the quantitative expression of the two forms did not significantly changed among patients. Furthermore, 3p/5p ratio was different between HB and non-HB samples, being positive in the latter and negative in HB samples. Influence of concomitant treatments in the expression of miR-483 (i.e. chemotherapy, and immunosuppressive drugs) was also evaluated and no changes were found in the follow-up. In conclusion the expression and function of miR-483-3p/5p in HB still remains unclear and further studies are needed to elucidate the possible mechanisms that regulate the different strand selection between the two forms of microRNA-483 in patients affected by HB. We deem that the analysis of microRNA-483 different forms could be useful for the molecular identification of HB patients and the discrimination with non-HB patient.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"196 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2016-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74975937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-01DOI: 10.4172/2157-7412.1000281
A. Benson, B. Shirts, A. Jacobson, C. Pritchard, T. Walsh, H. Jacob, Y. Goldberg
Purpose: To present a patient with familial adenomatous polyposis (FAP) caused by a low level of somatic mosaicism. Case description: A twenty-one year old female presented with rectal bleeding and abdominal pain. She underwent a colonoscopy and esophagogastroduodenoscopy which revealed extensive polyposis. There was no family history of polyps or early onset colon cancer in her family. Methodology: Next-generation sequencing (NGS) analysis was performed using the ColoSeqTM panel on DNA extracted from both peripheral blood lymphocytes and colonic polyps. RESULTS: Molecular analysis detected the p.E1408X deleterious mutation in the APC gene in in 12 of 276 (4%) reads of the DNA in the peripheral blood leukocytes and in 30% of the DNA from colonic polyps. Conclusion: We report that low level of 4% APC mosaicism led to florid polyposis. Our report highlights the power of deep next-generation sequencing to identify mosaic mutations that are missed by traditional approaches. Though somatic APC mosaicism has previously been reported to cause polyposis syndrome in a few cases, it has been underestimated as a cause of polyposis coli. This case should reinforce the need to search for mosaicism in all patients with a personal history of polyposis and no family history.
{"title":"Polyposis Caused by Low APC Mosaicism","authors":"A. Benson, B. Shirts, A. Jacobson, C. Pritchard, T. Walsh, H. Jacob, Y. Goldberg","doi":"10.4172/2157-7412.1000281","DOIUrl":"https://doi.org/10.4172/2157-7412.1000281","url":null,"abstract":"Purpose: To present a patient with familial adenomatous polyposis (FAP) caused by a low level of somatic mosaicism. Case description: A twenty-one year old female presented with rectal bleeding and abdominal pain. She underwent a colonoscopy and esophagogastroduodenoscopy which revealed extensive polyposis. There was no family history of polyps or early onset colon cancer in her family. Methodology: Next-generation sequencing (NGS) analysis was performed using the ColoSeqTM panel on DNA extracted from both peripheral blood lymphocytes and colonic polyps. RESULTS: Molecular analysis detected the p.E1408X deleterious mutation in the APC gene in in 12 of 276 (4%) reads of the DNA in the peripheral blood leukocytes and in 30% of the DNA from colonic polyps. Conclusion: We report that low level of 4% APC mosaicism led to florid polyposis. Our report highlights the power of deep next-generation sequencing to identify mosaic mutations that are missed by traditional approaches. Though somatic APC mosaicism has previously been reported to cause polyposis syndrome in a few cases, it has been underestimated as a cause of polyposis coli. This case should reinforce the need to search for mosaicism in all patients with a personal history of polyposis and no family history.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"69 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89786919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-01DOI: 10.4172/2157-7412.1000279
S. Vicari, F. Costanzo, Marco Arm, G. Carbonara, Pamela Varvara, C. Caciolo, C. Gagliardi, T. Gianesini, P. Alfieri, R. Capolino, D. Menghini
The occurrence and co-occurrence of psychiatric disorders have been more frequently reported in people with Intellectual Disability(ID) than in the general population. The present study was aimed at verifying whether the psychiatric profile of individuals with ID is just a consequence of ID or derives from a specific genotype. The psychiatric profile of 112 individuals with Down syndrome (DS) and 85 with Williams syndrome (WS) was examined. The interactions between psychiatric symptom clusters and the effect of age were also investigated. Participants with WS had higher rates of psychiatric disorders, and, specifically, of Anxiety disorders and Psychosis than DS. However, the psychiatric profile changed by age, since Anxiety disorder was higher in individuals with WS compared to DS in young age, while Psychosis in old age. A relation between the occurrence of disorders, as Anxiety disorder and Mood Disorder, was found only in participants with WS. Moreover, distinct Anxiety and Behavior Disorder subtypes emerged between groups. Results indicate that the genetic etiology of ID differently affects the psychiatric characteristics of the groups and suggest the importance of a targeted psychiatric care for individuals with WS and DS.
{"title":"Detecting Psychiatric Profile in Genetic Syndromes: A Comparison of Down Syndrome and Williams Syndrome","authors":"S. Vicari, F. Costanzo, Marco Arm, G. Carbonara, Pamela Varvara, C. Caciolo, C. Gagliardi, T. Gianesini, P. Alfieri, R. Capolino, D. Menghini","doi":"10.4172/2157-7412.1000279","DOIUrl":"https://doi.org/10.4172/2157-7412.1000279","url":null,"abstract":"The occurrence and co-occurrence of psychiatric disorders have been more frequently reported in people with Intellectual Disability(ID) than in the general population. The present study was aimed at verifying whether the psychiatric profile of individuals with ID is just a consequence of ID or derives from a specific genotype. The psychiatric profile of 112 individuals with Down syndrome (DS) and 85 with Williams syndrome (WS) was examined. The interactions between psychiatric symptom clusters and the effect of age were also investigated. Participants with WS had higher rates of psychiatric disorders, and, specifically, of Anxiety disorders and Psychosis than DS. However, the psychiatric profile changed by age, since Anxiety disorder was higher in individuals with WS compared to DS in young age, while Psychosis in old age. A relation between the occurrence of disorders, as Anxiety disorder and Mood Disorder, was found only in participants with WS. Moreover, distinct Anxiety and Behavior Disorder subtypes emerged between groups. Results indicate that the genetic etiology of ID differently affects the psychiatric characteristics of the groups and suggest the importance of a targeted psychiatric care for individuals with WS and DS.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"1 1","pages":"279"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83027483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-01DOI: 10.4172/2157-7412.1000277
V. Alesi, L. Bernardini, D. Goidin, M. Canestrelli, M. Dentici, Giuseppe Barrano, M. G. Giuffrida, A. Nardone, D. Postorivo, L. Laino, R. Genesio, B. Dallapiccola, A. Novelli
Over last decade chromosome microarray analysis has become a routine test, but its use as first tier in prenatal diagnosis still raises disputes specially when applied to low risk pregnancies. In order to limit the identification of incidental findings (IF) and variants of unknown significance (VOUS) we designed EasyChip, a low-resolution oligonucleotide array CGH platform with a functional resolution of 3 Mb in genomic backbone, 300 Kb in sub-telomeric regions, and 150 Kb in 43 regions associated with syndromic disorders, selected considering morbidity, penetrance, and etiological mechanisms. After an “in silico” evaluation, which showed that Easychip would not uncover most of VOUS (24% vs 3%) and any IF, we have validated EasyChip on 169 patients samples, 57 retrospective samples with known imbalances and 112 prospective samples as part of the prenatal diagnosis process. All the known rearrangements were detected and 7 further pathogenic imbalances were detected on the still undiagnosed cohort. To evaluate false positive/negative rate, thirty-eight out of the 112 prospective samples were also processed on an high resolution array CGH, allowing comparing the results in term of diagnostic utility and impact on detection rate. Two positive and pathogenic results were detected by both platforms. EasyChip did not detect 10 of the 11 VOUS nor 2 IF discovered by the high-resolution platform. In conjunction with karyotype, EasyChip is a useful tool in prenatal diagnosis for screening purposes on low risk pregnancies, it enables the detection of cryptic imbalanced subtelomeric rearrangements, microdeletions/duplications within 43 syndromic regions and supports standard cytogenetic analysis at whole genome level. Finally, this tool, differently from higher resolution platforms, significantly reduces the detection rate of VOUS and IF, which represent a major drawback during genetic counselling specially for low risk pregnancies, significantly reduces the time to spend on analysis and limit the need of additional confirmation.
{"title":"Easychip 8x15k: A New Tool for Detecting Chromosome Anomalies in Low Risk Pregnancies, Supporting and Integrating Standard Karyotype","authors":"V. Alesi, L. Bernardini, D. Goidin, M. Canestrelli, M. Dentici, Giuseppe Barrano, M. G. Giuffrida, A. Nardone, D. Postorivo, L. Laino, R. Genesio, B. Dallapiccola, A. Novelli","doi":"10.4172/2157-7412.1000277","DOIUrl":"https://doi.org/10.4172/2157-7412.1000277","url":null,"abstract":"Over last decade chromosome microarray analysis has become a routine test, but its use as first tier in prenatal diagnosis still raises disputes specially when applied to low risk pregnancies. In order to limit the identification of incidental findings (IF) and variants of unknown significance (VOUS) we designed EasyChip, a low-resolution oligonucleotide array CGH platform with a functional resolution of 3 Mb in genomic backbone, 300 Kb in sub-telomeric regions, and 150 Kb in 43 regions associated with syndromic disorders, selected considering morbidity, penetrance, and etiological mechanisms. After an “in silico” evaluation, which showed that Easychip would not uncover most of VOUS (24% vs 3%) and any IF, we have validated EasyChip on 169 patients samples, 57 retrospective samples with known imbalances and 112 prospective samples as part of the prenatal diagnosis process. All the known rearrangements were detected and 7 further pathogenic imbalances were detected on the still undiagnosed cohort. To evaluate false positive/negative rate, thirty-eight out of the 112 prospective samples were also processed on an high resolution array CGH, allowing comparing the results in term of diagnostic utility and impact on detection rate. Two positive and pathogenic results were detected by both platforms. EasyChip did not detect 10 of the 11 VOUS nor 2 IF discovered by the high-resolution platform. In conjunction with karyotype, EasyChip is a useful tool in prenatal diagnosis for screening purposes on low risk pregnancies, it enables the detection of cryptic imbalanced subtelomeric rearrangements, microdeletions/duplications within 43 syndromic regions and supports standard cytogenetic analysis at whole genome level. Finally, this tool, differently from higher resolution platforms, significantly reduces the detection rate of VOUS and IF, which represent a major drawback during genetic counselling specially for low risk pregnancies, significantly reduces the time to spend on analysis and limit the need of additional confirmation.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"13 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77670948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-11-27DOI: 10.4172/2157-7412.1000276
M. L. Coniglio, Cetica, Benedetta Ciambotti, S. Grieve, M. Pantaleo, C. Rizzari, E. Sieni, C. Favre, S. Giglio, G. Griffiths, M. Aricò
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening immune deficiency, characterized by a hyper-inflammatory syndrome. The familial form of HLH (FHL) is caused by mutations in genes associated with lymphocyte granule-mediated cytotoxicity. Mutations in STXBP2 (Sintaxin binding protein 2) gene result in defect of Munc18-2 protein, the causative defect of the subtype defined as FHL5. Functional tests as intracytoplasmic expression of perforin and surface expression of CD107a, help to direct genetic analysis. Different mutations have been described in the FHL-related genes known so far (PRF1, UNC13-D, STX11, STXBP2): missense, nonsense, splicing, regulatory, small deletions/insertions. Recently a pathogenic inversion of 253 KB upstream of the 3’ UNC13D gene has been reported. Here we describe a new deletion causative of FHL5. We confirmed the deletion by Real-Time PCR and by CGHarray. We finally documented by western blot the absence of expression of Munc18-2 protein in our patient. These data shows the need to introduce new diagnostic strategies in order to screen mutations not detected by the methods classically used.
{"title":"Identification of a Deletion in Stxbp2 Causative of Familial Hemophagocytic Lymphohistiocytosis Type 5","authors":"M. L. Coniglio, Cetica, Benedetta Ciambotti, S. Grieve, M. Pantaleo, C. Rizzari, E. Sieni, C. Favre, S. Giglio, G. Griffiths, M. Aricò","doi":"10.4172/2157-7412.1000276","DOIUrl":"https://doi.org/10.4172/2157-7412.1000276","url":null,"abstract":"Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening immune deficiency, characterized by a hyper-inflammatory syndrome. The familial form of HLH (FHL) is caused by mutations in genes associated with lymphocyte granule-mediated cytotoxicity. Mutations in STXBP2 (Sintaxin binding protein 2) gene result in defect of Munc18-2 protein, the causative defect of the subtype defined as FHL5. Functional tests as intracytoplasmic expression of perforin and surface expression of CD107a, help to direct genetic analysis. Different mutations have been described in the FHL-related genes known so far (PRF1, UNC13-D, STX11, STXBP2): missense, nonsense, splicing, regulatory, small deletions/insertions. Recently a pathogenic inversion of 253 KB upstream of the 3’ UNC13D gene has been reported. Here we describe a new deletion causative of FHL5. We confirmed the deletion by Real-Time PCR and by CGHarray. We finally documented by western blot the absence of expression of Munc18-2 protein in our patient. These data shows the need to introduce new diagnostic strategies in order to screen mutations not detected by the methods classically used.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"137 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2015-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84034730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-11-19DOI: 10.4172/2157-7412.1000274
M. Zargar, T. M. Malla, F. Dar
The present study was proposed to unveil the incidence and pattern of chromosomal abnormalities in recurrent spontaneous abortion couples of Kashmir, North India. A total of 71 couples within the age group of 24 to 42 years and having history of two or more recurrent spontaneous abortions were included in the study. Peripheral blood lymphocyte cultures were set for each subject according to standard protocol and chromosomal analysis was carried out on well spread metaphases by the help of Cytovision software Version 3.9. The incidence of chromosomal abnormalities in spontaneous abortion couples of this region was found to be 7.75% that include numerical (1.40%) as well as structural (7.75%) chromosomal abnormalities. Both males (2.11%) and females (5.63%) possessed chromosomal aberrations that comprised balanced translocations (4.22%), duplications (0.70%), deletions (0.70%) and inversions (2.11%). Besides, We report three unique balanced translocations viz., t(1;3)(q24.3;p25)(1 case); t(6,16)(p11;q23)(1 case) and t(7;14)(p13;q12)(2 cases). that have not been found elsewhere in the literature. We conclude from the present study that chromosomal alterations do occur as an etiology in the RSA couples of Kashmir and their incidence is consistent with many reports around the world. The precise molecular characterization of the unique breakpoint regions reported in our study could help in identification of new genes involved in recurrent spontaneous abortions. The study being the first of its kind in this part of the world forms the basis for further studies of the couples of this region with recurrent spontaneous abortions.
本研究旨在揭示北印度克什米尔地区复发性自然流产夫妇染色体异常的发生率和模式。共有71对年龄在24至42岁之间且有两次或两次以上复发性自然流产史的夫妇被纳入研究。按照标准方案对每位受试者进行外周血淋巴细胞培养，利用Cytovision Version 3.9软件对扩散良好的中期进行染色体分析。本地区自然流产夫妇染色体异常发生率为7.75%，包括数字染色体异常(1.40%)和结构染色体异常(7.75%)。男性(2.11%)和女性(5.63%)的染色体畸变包括平衡易位(4.22%)、重复(0.70%)、缺失(0.70%)和倒位(2.11%)。此外，我们报告了三个独特的平衡易位，即t(1;3)(q24.3;p25)(1例);t(16)(赛;q23处)(1例)和t (7; 14) (p13; q12)(2例)。这在其他文献中没有发现。我们从目前的研究中得出结论，染色体改变确实发生在克什米尔的RSA夫妇中，其发病率与世界各地的许多报道一致。在我们的研究中报道的独特断点区域的精确分子特征可以帮助鉴定与复发性自然流产有关的新基因。该研究是世界上第一个此类研究，为进一步研究该地区复发性自然流产夫妇奠定了基础。
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