Indian journal of human genetics最新文献

{"title":"Innumerable studies on single nucleotide polymorphisms: What could be its utility?","authors":"K Ghosh, Ajit Gorakshakar","doi":"10.4103/0971-6866.124354","DOIUrl":"10.4103/0971-6866.124354","url":null,"abstract":"","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 4","pages":"381-3"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fb/7c/IJHG-19-381.PMC3897129.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32090253","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":"Molecular characterization in a case of isolated growth hormone deficiency and further prenatal diagnosis of an unborn sibling.","authors":"Ruchi Nadar,&nbsp;Kavita Khatod,&nbsp;Nikhil Phadke,&nbsp;Chaitanya Datar,&nbsp;Sujata Vaidya,&nbsp;Anuradha Khadilkar,&nbsp;Vaman Khadilkar","doi":"10.4103/0971-6866.124380","DOIUrl":"https://doi.org/10.4103/0971-6866.124380","url":null,"abstract":"<p><p>Familial isolated growth hormone deficiency (GHD) type 1 is characterized by an autosomal recessive pattern of inheritance with varying degrees of phenotypic severity. We report a proband, with isolated GHD (IGHD) with very early growth arrest and undetectable levels of GH. Homozygous complete deletion of the GH1 gene was identified by real-time/quantitative polymerase chain reaction (RT/q-PCR) and confirmed by an independent molecular genetic method; the multiplex ligation-dependent probe amplification (MLPA) technique. Prenatal diagnosis was offered for the subsequent pregnancy in the mother of our proband. Identical heterozygous deletion of the GH1 gene was detected in both parents. The fetus had a similar homozygous deletion of the GH1 gene. We thus report a unique case with a confirmed mutation in GH1 gene in the proband followed by prenatal detection of the same mutation in the amniotic fluid which to our knowledge hitherto has not been documented from India. </p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 4","pages":"475-8"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.124380","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32090636","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":"An incidental case of dihydropyrimidine dehydrogenase deficiency: One case, multiple challenges.","authors":"Hamoud H Al Khallaf,&nbsp;Miao He,&nbsp;Angela Wittenauer,&nbsp;Elizabeth E Woolley,&nbsp;Mariagrazia Cunto,&nbsp;Muhammad Ali Pervaiz","doi":"10.4103/0971-6866.124382","DOIUrl":"https://doi.org/10.4103/0971-6866.124382","url":null,"abstract":"<p><p>Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disorder that shows large phenotypical variability, ranging from no symptoms to intellectual disability, motor retardation, and convulsions. In addition, homozygous and heterozygous mutation carriers can develop severe 5-fluorouracil (5-FU) toxicity. The lack of genotype-phenotype correlation and the possibility of other factors playing a role in the manifestation of the neurological abnormalities, make the management and education of asymptomatic DPD individuals more challenging. We describe a 3-month-old baby who was incidentally found by urine organic acid testing (done as part of positive newborn screen) to have very high level of thymine and uracil, consistent with DPD deficiency. Since the prevalence of asymptomatic DPD deficiency in the general population is fairly significant (1 in 10,000), we emphasize in this case study the importance of developing a guideline in genetic counseling and patient education for this condition as well as other incidental laboratory findings. </p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 4","pages":"483-6"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.124382","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32090638","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":"A case report of ectopia cordis and omphalocele.","authors":"Amar M Taksande,&nbsp;Krishna Y Vilhekar","doi":"10.4103/0971-6866.124384","DOIUrl":"https://doi.org/10.4103/0971-6866.124384","url":null,"abstract":"<p><p>A rare congenital defect in fusion of the anterior chest wall resulting in an extrathoracic location of the heart. Cantrell's pentalogy is a congenital anomaly resulting from embryologic development defect and consists of the following: A deficiency of the anterior diaphragm, a midline supraumbilical abdominal wall defect, a defect in the diaphragmatic pericardium, congenital intracardiac abnormalities, and a defect of the lower sternum. Here we report a rare case of ectopic cordis with omphalocele. </p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 4","pages":"491-3"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.124384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32090640","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":"Protein tyrosine phosphatase non-receptor type 22 gene polymorphism C1858T is not associated with leprosy in Azerbaijan, Northwest Iran.","authors":"Mohammad Reza Aliparasti,&nbsp;Shohreh Almasi,&nbsp;Jafar Majidi,&nbsp;Fatemeh Zamani,&nbsp;Ali Reza Khoramifar,&nbsp;Ali Reza Farshi Azari","doi":"10.4103/0971-6866.124365","DOIUrl":"https://doi.org/10.4103/0971-6866.124365","url":null,"abstract":"<p><strong>Background: </strong>Leprosy (Hansen's disease) is a human chronic granulomatous infectious disease caused by Mycobacterium leprae. Several types of study support a role for host genetics in susceptibility to leprosy. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an intracellular lymphoid protein tyrosine phosphatase that has been shown to play a negative regulatory role in T-cell activation.</p><p><strong>Aims: </strong>The aim of the present study was to find out associating the PTPN22 C1858T (R620W) polymorphism and leprosy in the Azeri population from Northwest Iran.</p><p><strong>Materials and methods: </strong>A total of 153 treated leprosy patients and 197 healthy and ethnic matched controls entered this study. We used restriction fragment length polymorphism method to type PTPN22 C1858T polymorphism.</p><p><strong>Results: </strong>There was no significant difference in distribution of genotype and allele frequencies of PTPN22 C1858T polymorphism between leprosy patients and controls (P = 0.641 and 0.645; respectively). Moreover, there was no significant association between different clinical findings (karnofsky performance status score, clinical forms and manifestations of leprosy) and PTPN22 C1858T polymorphism. Data showed a low frequency of the minor (T) allele by 2.3% in leprosy and 1.5% in healthy individuals.</p><p><strong>Conclusions: </strong>The PTPN22 C1858T (R620W) is not relevant in susceptibility to leprosy in the Azeri population of Northwest Iran.</p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 4","pages":"403-7"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.124365","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32090257","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":"Promoter variants in interleukin-6 and tumor necrosis factor alpha and risk of coronary artery disease in a population from Western India.","authors":"Aparna A Bhanushali,&nbsp;B R Das","doi":"10.4103/0971-6866.124371","DOIUrl":"https://doi.org/10.4103/0971-6866.124371","url":null,"abstract":"<p><strong>Introduction: </strong>A central component of the atherosclerotic process is inflammation. Single nucleotide polymorphisms (SNPs) present in the promoter region of various cytokines can lead to altered levels of the transcript and a state of low-grade inflammation exacerbating the risk of coronary artery disease (CAD). The present work tries to understand the role of permissive promoter variants in the interleukin-6 gene (IL-6-174G/C) and the tumor necrosis factor alpha (TNFα-308G/A) in the causation of CAD and also dyslipidemia.</p><p><strong>Materials and methods: </strong>Genotyping was conducted on 100 cases of CAD and 150 controls by the allele termination assay SNaPshot. Biochemical parameters were determined by routine enzymatic endpoint methods. The results were analyzed by appropriate statistical methods.</p><p><strong>Results: </strong>No differences in the minor allele frequency IL-6-174G/C SNP were seen between cases and controls (0.13 vs. 0.12). The differences in the allele frequency of TNFα-308A between cases (6%) and controls (2%) have led to an odds ratio, 3.370; 95% confidence interval, 1.039-11.543; P=0.033 in the univariate analysis. In the final logistic regression analysis, however none of the variants were associated with an increased risk of CAD.</p><p><strong>Conclusions: </strong>In summary, no association of the permissive promoter variants in the IL-6 gene and the TNFα gene were seen with an increased CAD risk. These and other studies highlight the importance of doing population specific studies.</p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 4","pages":"430-6"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.124371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32090696","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":"Genomic characterization of some Iranian children with idiopathic mental retardation using array comparative genomic hybridization.","authors":"Farkhondeh Behjati, Saghar Ghasemi Firouzabadi, Roxana Kariminejad, Roshanak Vameghi, Firouzeh Sajedi, Yousef Shafaghati, Behruz Ebrahimizade Ghasemlou, Azadeh Shojaei, Peyman Jamali, Ideh Bahman, Hossein Najmabadi","doi":"10.4103/0971-6866.124373","DOIUrl":"10.4103/0971-6866.124373","url":null,"abstract":"<p><strong>Background: </strong>Mental retardation (MR) has a prevalence of 1-3% and genetic causes are present in more than 50% of patients. Chromosomal abnormalities are one of the most common genetic causes of MR and are responsible for 4-28% of mental retardation. However, the smallest loss or gain of material visible by standard cytogenetic is about 4 Mb and for smaller abnormalities, molecular cytogenetic techniques such as array comparative genomic hybridization (array CGH) should be used. It has been shown that 15-25% of idiopathic MR (IMR) has submicroscopic rearrangements detectable by array CGH. In this project, the genomic abnormalities were investigated in 32 MR patients using this technique.</p><p><strong>Materials and methods: </strong>Patients with IMR with dysmorphism were investigated in this study. Karyotype analysis, fragile X and metabolic tests were first carried out on the patients. The copy number variation was then assessed in a total of 32 patients with normal results for the mentioned tests using whole genome oligo array CGH. Multiple ligation probe amplification was carried out as a confirmation test.</p><p><strong>Results: </strong>In total, 19% of the patients showed genomic abnormalities. This is reduced to 12.5% once the two patients with abnormal karyotypes (upon re-evaluation) are removed.</p><p><strong>Conclusion: </strong>The array CGH technique increased the detection rate of genomic imbalances in our patients by 12.5%. It is an accurate and reliable method for the determination of genomic imbalances in patients with IMR and dysmorphism.</p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 4","pages":"443-8"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/80/27/IJHG-19-443.PMC3897140.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32090698","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 variants in the cytochrome P450 2D6 gene in the Sri Lankan population.","authors":"T D Praveen Tharanga,&nbsp;C M V Jinadasa,&nbsp;M F Risama,&nbsp;Priyadarshani Galappatthy,&nbsp;R L Jayakody,&nbsp;Vajira H W Dissanayake","doi":"10.4103/0971-6866.124361","DOIUrl":"https://doi.org/10.4103/0971-6866.124361","url":null,"abstract":"<p><strong>Introduction: </strong>Cytochrome P450 2D6 (CYP2D6) enzymes are involved in the metabolism of a large number of commonly prescribed drugs such as antidepressants and cardiovascular drugs. The CYP2D6 *3, *4 and *14 variants associated with the loss of enzyme function; CYP2D6 *10 and *17 variants with reduced enzyme function; and CYP2D6 *2 variant with no effect on enzyme function. Establishing the frequency of these variant alleles in Sri Lankan population would be useful for optimizing pharmacotherapy with CYP2D6-substrate drugs.</p><p><strong>Objective: </strong>The objective of this study was to determine the prevalence of CYP2D6 *2, *3, *4, *10, *14 and *17 variants in the main ethnic groups in the Sri Lankan population.</p><p><strong>Materials and methods: </strong>A total of 90 deoxyribonucleic acid (DNA) samples (30 each from Sinhalese, Tamils and Moors) were selected from a DNA resource at the Human Genetic Unit, Faculty of Medicine, University of Colombo. This collection had been made for population genetic studies from a random population based volunteers. Genotyping was performed using published polymerase chain reaction/restriction fragment length polymorphism methods.</p><p><strong>Results: </strong>The prevalence of the CYP2D6 variants in Sinhalese, Sri Lankan Tamils and Moors respectively were CYP2D6 *2: 37%, 41.6% and 37.9%; CYP2D6 *3: 60.3%, 45% and 30%; CYP2D6 *4: 21.6%, 6.6% and 8.3%; CYP2D6 *10: 40%, 35% and 44%. CYP2D6 *14 and *17 variants were not identified.</p><p><strong>Conclusion: </strong>CYP2D6*3, *4 and *10 variants, which are associated with reduced or loss of CYP2D6 enzyme function were found in our population in significant frequencies. CYP2D6*4, which is reported to be a Caucasian variant was also found in all three ethnic groups.</p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 4","pages":"392-6"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.124361","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32090255","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 polymorphisms of estrogen receptor alpha and catechol-O-methyltransferase genes in Turkish patients with familial prostate carcinoma.","authors":"Ayfer Pazarbasi,&nbsp;M Bertan Yilmaz,&nbsp;Davut Alptekin,&nbsp;Umit Luleyap,&nbsp;Zuhtu Tansug,&nbsp;Lutfiye Ozpak,&nbsp;Muzeyyen Izmirli,&nbsp;Dilge Onatoglu-Arikan,&nbsp;Sabriye Kocaturk-Sel,&nbsp;Mehmet Ali Erkoc,&nbsp;Ozgur Turgut,&nbsp;Ceyhun Bereketoglu,&nbsp;Erdal Tunc,&nbsp;Eylul Akbal","doi":"10.4103/0971-6866.124366","DOIUrl":"https://doi.org/10.4103/0971-6866.124366","url":null,"abstract":"<p><strong>Objectives: </strong>Estrogen is one of the most crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. We evaluated the association between genetic polymorphisms in estrogen receptor alpha (ESR1) and catechol-O-methyltransferase (COMT) genes and the risk of developing familial prostate carcinoma.</p><p><strong>Materials and methods: </strong>In this study, 34 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 30 healthy age-matched male controls were enrolled. The genotypes of ESR1 and COMT genes were analyzed employing polymerase chain reaction-restriction fragment length polymorphism method. 34 cases with prostate carcinoma, whose first degree relatives had prostate carcinoma and 14 age-matched male controls were enrolled to analyze the genotype of these two genes.</p><p><strong>Results: </strong>Among control patients, the ESR1 PvuII genotypes of C/C, C/T and T/T were observed in 37%, 26% and 37%, respectively, whereas the C/C, C/T and T/T genotypes were observed in 18%, 41% and 41% of case patients, respectively. Among controls, the ESR1 PvuII allele frequencies of C and T were equally observed, whereas the C and T allele frequencies were observed in 38% and 62% of patients, respectively. Among ESR1 PvuII genotypes there were not any significant difference in terms of genotype (P = 0.199) and allele (P = 0.181) frequencies. Among controls, the ESR1 XbaI genotypes of G/G, G/A and A/A were observed in 33%, 37% and 33%, respectively, whereas the G/G, G/A and A/A genotypes were observed in 12%, 47% and 41% of patients, respectively. Among controls, the ESR1 XbaI allele frequencies of A and G were observed equally, respectively, whereas the A and G frequencies were observed in 65% and 35% of patients, respectively. Among ESR1 Χ baI, there was not any significant difference in terms of genotype (P = 0.111) and allele (P = 0.093) frequencies. But the C/C genotype of the PvuII site and G/G genotype of the XbaI site in the ESR1 gene were associated significantly with the risk of developing prostate carcinoma. The G/G, G/A and A/A genotypes of the COMT gene were observed in 50%, 29% and 21% of control patients and in 53%, 21% and 26% of case patients, respectively. The A and G allele frequencies of the COMT gene were observed in 36.7%, 63.3% of control patients and in 36.8%, 63.2% of case patients, respectively. In COMT gene, there was not any significant difference in terms of genotype (P = 0.843) and allele (P = 0.991) frequencies. But the G/A genotype of the COMT gene had a weak tendency toward increased risk.</p><p><strong>Conclusion: </strong>Polymorphisms of ESR1 gene in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low-penetrance genes are targets for ","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 4","pages":"408-11"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.124366","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32090258","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":"Double heterozygous hemoglobin Q India/hemoglobin D Punjab hemoglobinopathy: Report of two rare cases.","authors":"Deepti Mutreja,&nbsp;Seema Tyagi,&nbsp;Narender Tejwani,&nbsp;Jasmita Dass","doi":"10.4103/0971-6866.124381","DOIUrl":"https://doi.org/10.4103/0971-6866.124381","url":null,"abstract":"<p><p>Cation exchange high performance liquid chromatography (CE HPLC) provides an excellent tool for accurate and reliable diagnosis of various hemoglobin (Hb) disorders. HbQ India is a rare alpha chain variant that usually presents in the heterozygous state. Its presence in double heterozygous state with HbD Punjab is extremely rare. The double heterozygosity for α and β chain variants leads to formation of abnormal heterodimer hybrids, which can lead to diagnostic dilemmas. We report two rare cases of double heterozygous HbQ India/HbD Punjab where the hybrid Hb was seen to elute at retention time similar to HbC on CE HPLC. The first case had unconjugated hyperbilirubinemia at presentation; while, the second case was asymptomatic. </p>","PeriodicalId":88516,"journal":{"name":"Indian journal of human genetics","volume":"19 4","pages":"479-82"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/0971-6866.124381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32090637","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}