Indian journal of human genetics最新文献

{"title":"Type 2 diabetes mellitus: An unusual association with Down's syndrome.","authors":"Sunil Kumar Kota,&nbsp;Prabhas Ranjan Tripathy,&nbsp;Siva Krishna Kota,&nbsp;Sruti Jammula","doi":"10.4103/0971-6866.120818","DOIUrl":"https://doi.org/10.4103/0971-6866.120818","url":null,"abstract":"<p><p>Down's syndrome (DS) is known to be associated with autoimmune disease including type 1 diabetes. To the best of our knowledge, there are no reports of DS with type 2 diabetes mellitus in the literature. We hereby report two cases of DS with type 2 diabetes. </p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 3","pages":"358-9"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.120818","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31956245","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}

{"title":"Genetic mutations in Gorlin-Goltz syndrome.","authors":"Muthumula Daneswari, Mutjumula Swamy Ranga Reddy","doi":"10.4103/0971-6866.120810","DOIUrl":"10.4103/0971-6866.120810","url":null,"abstract":"<p><p>Gorlin-Goltz syndrome is a rare multisystemic disease inherited in a dominant autosomal at a high level of penetrance and variable expressiveness. It is mainly characterized by basal cell carcinoma, odontogenic keratocyst and skeletal anomalies. Diagnosis is based upon established major and minor clinical and radiographic criteria and gene mutation analysis. This article presents a case of Gorlin-Goltz syndrome, its genetic predisposition, diagnosis and management. </p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 3","pages":"369-72"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8c/c2/IJHG-19-369.PMC3841570.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31956249","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}

{"title":"Novel three missense mutations observed in Von Hippel-Lindau gene in a patient reported with renal cell carcinoma.","authors":"Pasupuleti Santhosh Kumar,&nbsp;Katari Venkatesh,&nbsp;Lokanathan Srikanth,&nbsp;Potukuchi Venkata Gurunadha Krishna Sarma,&nbsp;Akkamgari Ramprasad Reddy,&nbsp;Srinivasan Subramanian,&nbsp;Bobbidi Venkata Phaneendra","doi":"10.4103/0971-6866.120809","DOIUrl":"https://doi.org/10.4103/0971-6866.120809","url":null,"abstract":"<p><p>Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary cancer syndrome that predisposes to the development of a variety of benign and malignant tumors, especially cerebellar hemangioblastomas, retinal angiomas and clear-cell renal cell carcinomas (RCC). We have identified of VHL gene using immunohistochemistry in a patient who was diagnosed for RCC. In order to understand the involvement of mutation in the VHL gene exon 1 was amplified and sequenced (accession number: JX 401534). The sequence analysis revealed the presence of novel missense mutations c.194 C>T, c.239 G>A, c.278 G>A, c.319 C>G, c. 337 C > G leading to the following variations p.Ala 65 Val, p.Gly 80 Asp, p.Gly 93 Glu, p.Gln 107 Glu, p.Gln 113 Glu in the protein. </p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 3","pages":"373-6"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.120809","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31955696","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}

{"title":"Warfarin pharmacogenetics: How close are we to clinical practice?","authors":"Tejasvita Gaikwad,&nbsp;Shrimati Shetty,&nbsp;Kanjaksha Ghosh","doi":"10.4103/0971-6866.120806","DOIUrl":"https://doi.org/10.4103/0971-6866.120806","url":null,"abstract":"The past decade has seen substantial advances in our understanding of the genetic factors influencing response to a variety of drugs including warfarin. Though there has been an increase in the clinical use of pharmacogenetic information to individualize treatment regimens, yet there generally has not been broad acceptance of pharmacogenetic testing. Warfarin remains the mainstay therapy for oral anticoagulation; it also remains one of the most challenging medications to manage despite over 60 years of experience with the drug. It is one of the top 10 drugs related to adverse drug events and hospitalization. Clinical management of warfarin therapy mainly is complicated by a narrow therapeutic index and high inter‐ and intra‐individual variability in drug disposition and response. Supratherapeutic international normalized ratio (INRs) can lead to fatal hemorrhage while subtherapeutic INRs can lead to thrombosis. Growing evidence indicates that up to 60% of the individual pharmacological response to warfarin might be due to genetic variables and affected by polymorphisms in the genes mainly, vitamin K epoxide reductase complex subunit 1 (VKORC1), the target enzyme of warfarin and cytochrome P450 2C9 (CYP2C9), the main enzyme involved in warfarin metabolism. Although the genotypes of VKORC1 and CYP2C9 are clearly the most important genetic factors for warfarin response, genetic variations in other genes for instance, CYP4F2 and GGCX also show significant association with warfarin response. Non‐genetic factors such as age (elderly patients), diet (vitamin K rich diet), disease states (thyroid activity, liver or renal dysfunction, fever), other drugs (e.g., amiodarone, propafnone, metronidazole, tamoxifen, etc.), life‐style (alcohol intake, smoking, exercise) can also substantially modulate the response to warfarin. VKORC1 polymorphisms have been reported to be more potent modifiers of warfarin response than the CYP2C9 polymorphisms. Recent work by Rieder et al.[1] has also shown that individuals with VKORC1 A haplotype (H1 and H2) require low warfarin dose as a result of a decreased expression of messenger ribonucleic acid when compared to individuals with VKORC1 B haplotype (H7, H8 and H9). In the present issue of the journal, Kumar et al.[2] have studied genotype, allele and haplotype frequencies of VKORC1 and CYP4F2 in South Indian population. The authors have used 5 VKORC1 single nucleotide polymorphisms (SNPs) (similar to the report by Rieder et al.) to draw the VKORC1 haplotypes and the haplotype frequency has been compared with that of other populations. Except two SNPs, a strong LD pattern (D’ > 0.8) has been observed in this study for all the remaining studied SNPs in VKORC1 gene. In addition, the genotype frequencies of CYP4F2 were also found to be distinct in Indian population when compared to the rest of the populations. Thus, the study further","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 3","pages":"277-8"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.120806","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31955370","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}

{"title":"Possible impact of factor V Leiden genotype on warfarin induced bleeding.","authors":"Tejasvita Gaikwad,&nbsp;Kanjaksha Ghosh,&nbsp;Shrimati Shetty","doi":"10.4103/0971-6866.120807","DOIUrl":"https://doi.org/10.4103/0971-6866.120807","url":null,"abstract":"We read with interest the report, recently published by Nahar et al.[1] on the prevalence of warfarin sensitive alleles in factor V Leiden (FVL) mutation carriers. The study provides preliminary evidence for the need of pre‐prescription genotyping of warfarin sensitive polymorphisms (CYP2C9*2, *3 and Vitamin‐K epoxide reductase complex subunit1 [VKORC1]‐1639G/A) in patients who are at risk of thrombosis (carriers of thrombophilic marker) and require anticoagulation therapy.","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 3","pages":"377-8"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.120807","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31955697","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}

{"title":"Genetic and molecular analysis of the CLDN14 gene in Moroccan family with non-syndromic hearing loss.","authors":"Majida Charif,&nbsp;Redouane Boulouiz,&nbsp;Amina Bakhechane,&nbsp;Houda Benrahma,&nbsp;Halima Nahili,&nbsp;Abdelmajid Eloualid,&nbsp;Hassan Rouba,&nbsp;Mostafa Kandil,&nbsp;Omar Abidi,&nbsp;Guy Lenaers,&nbsp;Abdelhamid Barakat","doi":"10.4103/0971-6866.120828","DOIUrl":"https://doi.org/10.4103/0971-6866.120828","url":null,"abstract":"<p><strong>Background: </strong>Hearing loss is the most prevalent human genetic sensorineural defect. Mutations in the CLDN14 gene, encoding the tight junction claudin 14 protein expressed in the inner ear, have been shown to cause non-syndromic recessive hearing loss DFNB29.</p><p><strong>Aim: </strong>We describe a Moroccan SF7 family with non-syndromic hearing loss. We performed linkage analysis in this family and sequencing to identify the mutation causing deafness.</p><p><strong>Materials and methods: </strong>Genetic linkage analysis, suggested the involvement of CLDN14 and KCNE1 gene in deafness in this family. Mutation screening was performed using direct sequencing of the CLDN14 and KCNE1 coding exon gene.</p><p><strong>Results: </strong>Our results show the presence of c.11C>T mutation in the CLDN14 gene. Transmission analysis of this mutation in the family showed that the three affected individuals are homozygous, whereas parents and three healthy individuals are heterozygous. This mutation induces a substitution of threonine to methionine at position 4.</p><p><strong>Conclusion: </strong>These data show that CLDN14 gene can be i mplicated in the development of hearing loss in SF7 family; however, the pathogenicity of c.11C>T mutation remains to be determined.</p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 3","pages":"331-6"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.120828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31956238","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}

{"title":"Mosaic double aneuploidy: Down syndrome and XYY.","authors":"Mayur Parihar,&nbsp;Beena Koshy,&nbsp;Vivi Miriam Srivastava","doi":"10.4103/0971-6866.120825","DOIUrl":"https://doi.org/10.4103/0971-6866.120825","url":null,"abstract":"<p><p>Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5-year-old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21[19]/48, XYY,+21[6]. ish XYY (DXZ1 × 1, DYZ1 × 2). Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management. </p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 3","pages":"346-8"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.120825","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31956241","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}

{"title":"Hemoglobin E disorder: Newborn screening program.","authors":"Viroj Wiwanitkit","doi":"10.4103/0971-6866.120808","DOIUrl":"https://doi.org/10.4103/0971-6866.120808","url":null,"abstract":"<p><p>Hemoglobin E (Hb E) disorder is an important kind of hemoglobinopathy. It can be seen around the world with the highest prevalence in Southeast Asia. The screening for this disorder becomes the public health policies in many countries. The screening can be performed in several population groups. The newborn screening program for Hb E disorder is an important issue in pediatric genetics. In this brief review, the author discusses on important laboratory tests for screening for Hb E disorder in newborn. </p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 3","pages":"279-81"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.120808","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31955371","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}

{"title":"Polymorphism at P21 codon 31 and dinucleotide polymorphism of P73 gene and susceptibility to bladder cancer in individuals from North India.","authors":"Praveen Kumar Jaiswal,&nbsp;Vibha Singh,&nbsp;Rama Devi Mittal","doi":"10.4103/0971-6866.120815","DOIUrl":"https://doi.org/10.4103/0971-6866.120815","url":null,"abstract":"<p><strong>Background and aim: </strong>p73, a novel P53 homolog and plays an important role in modulating cell cycle control, apoptosis and cell growth while P21, functions to negatively control the cell cycle. P53 up regulates p21 expression in response to deoxyribonucleic acid damage leading to cell cycle arrest at G1 checkpoint. In the present study, we are targeting p21 codon 31 and p73 gene variants of G4C14-to-A4T14 (Exon 2) polymorphism for bladder cancer (BC) risk in North Indians.</p><p><strong>Materials and methods: </strong>The above gene variants of P21 and P73 were assessed in the case-control study comprising of 200 BC cases and 200 healthy controls of the same age, gender and similar ethnicity. Genotyping was performed by polymerase chain reaction (PCR) restriction fragment length polymorphism method and PCR-based confronting two-pair primers (PCR with CTPP).</p><p><strong>Results: </strong>The variant genotype of p73Exon 2 polymorphism showed significant risk for BC (p = 0.014). While combining with heterozygous genotype, variant genotype of p73Exon2 showed a significant association with BC risk (p = 0.010). While in case of p21 codon31 showed no significant association for BC risk at genotypic level. Significant association between p73Exon2 polymorphism and smoking was observed for BC risk. Furthermore, gene combination analysis revealed that AT/AT-Ser/Ser is associated with risk for BC. Variant genotype of P73Exon2 was associated with reduced risk of recurrence (p = 0.039) in superficial BC patients receiving Bacillus Calmette-Guerin treatment thus showing least survival (log rank = 0.029).</p><p><strong>Conclusion: </strong>Our study provided evidence that the p73 G4C14 > A4T14 (Exon2) polymorphisms were associated with higher risk of BC in North Indian population.</p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 3","pages":"293-300"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.120815","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31956296","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}

{"title":"Linkage study of DFNB3 responsible for hearing loss in human.","authors":"Akhtar Ali,&nbsp;Masroor E Babar,&nbsp;Saeeda Kalsoom,&nbsp;Jamil Ahmad,&nbsp;Kamran Abbas","doi":"10.4103/0971-6866.120827","DOIUrl":"https://doi.org/10.4103/0971-6866.120827","url":null,"abstract":"<p><strong>Background: </strong>Hearing disorders represent a significant health problem worldwide. Recessive inherited cases of the deafness are more prevalent in Pakistan due to consanguineous marriages. Deafness caused by DFNB3 is due to mutation in the gene MYO XVA and its prevalence among Pakistani population is about 5%.</p><p><strong>Materials and methods: </strong>Families with at least two or more individual affected with deafness were selected from different areas of District Okara of Pakistan. Six consanguineous families of different ethnic groups having deaf individuals were studied. All these families had three or more deaf individuals in either two or more sib ships. Family history was taken to minimize the chances of other abnormalities. Pedigrees drawn by using Cyrillic software (version 2.1) showed that all the marriages were consanguineous and the families have recessive mode of inheritance. Three STR markers were selected and amplified on all the samples of six families through PCR. The PCR products were then genotyped on non denaturing polyacrylamide gel electrophoresis (PAGE). Haplotypes were constructed to determine the pattern of inheritance and also to determine whether a family was linked or unlinked with known DFNB3 locus.</p><p><strong>Results: </strong>One out of six families showed linkage to the DFNB3 while rest of the families remained unlinked. Carriers of deafness genes were identified and information was provided to the families on request.</p><p><strong>Conclusion: </strong>Knowledge about the genetic causes of deafness provide insight into the variable expression of genes involved in this hereditary problem and may allow the prediction and prevention of associated health problems.</p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 3","pages":"325-30"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.120827","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31956301","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}