Ambiguous Genitalia, a rare genetic disorder is caused by defects in the process of fetal sexual determination and differentiation where a newborn needs prompt evaluation to detect lethal conditions and gender assignment. This genetic screening is taken up with an aim to evaluate the prevalence of the patients born with Ambiguous Genitalia existing in our population.
Background: Cystic Fibrosis (CF) one of the most common severe autosomal recessive disorders is caused by mutations in CFTR gene. The mutation distributions vary widely between different geographical and ethnic groups. In view of ethnic nature of Kashmiri population (North India), we aim at looking for the 3 common mutations Δ508, 3849+10 kb, C>T and W1282X in CF suspected cases.
Method:The mutations were evaluated in 150 highly suspected children with CF, proven by clinical features. ARMS-PCR was used for mutation detection of Δ508 and W1282X while as 3849+10 kb, C>T was assessed by indigenously developed ARMS-PCR and results were confirmed by RFLP.
Results:Of the 150 suspected CF cases, one of the three mutations was found in 60 out of the 300 alleles genotyped. Δ508 mutation was found in 36 of 150 (24%) cases, 3849+10 kb, C>T in 24 of 150(16%) cases while as no mutation was observed in W1282X. Interestingly 08 of 09 samples with normal sweat chloride were detected positive for 3849+10 kb, C>T mutation.
Conclusion:In this report, frequency of the Δ508 mutation in Kashmiri children with CF is less as compared to the Western Countries. Interestingly, we identified 3849+10 kb, C>T mutation as unique in population under study with much higher frequency as compared to rest of the world. Further we found intron 19, 3849+10 kb, C>T mutation serves as marker in those CF cases having sweat chloride negative.
SummaryBackground: Studies have demonstrated that the mutant *2 and*3 allele of the CYP2C19 loss-of-function polymorphism is associated with diminished metabolization of clopidogrel and an attenuated platelet response to clopidogrel treatment. Since no such study has been conducted in this region, we examined CYP2C19 polymorphism in Acute Coronary Syndrome (ACS) patients on clopidogrel treatment, and its effect on the cardiovascular outcomes.
Material and Methods:A total of 100 samples of ACS were included in this study and genotyping of CYP2C19 *2 and *3 gene polymorphisms was performed by a Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP).
Results:The distribution of CYP2C19*2 allele wild *1/*1, Heterozygous *1/*2 and homozygous mutant *2/*2 genotypes was 56%, 34% and 10% respectively while for CYP2C19*3 wild*1/*1 and heterozygous *1/*3 genotypes was 84% and 16% respectively. The frequency of compound heterozygotes (*2/*3) was found in 9% (9 of 100 patients). CYP2C19 *1/*2 allele was found in 03 of 34 (8.8%) patients who had CV events followed by 2 of 10 (20%) patients with mutant genotype CYP2C19*2 (*2/*2) on follow up. In the CYP2C19*3, 31.2% having heterozygous genotype (*1/*3) had CV events as compared to 11.9% with *1/*1 (31% v/s 11.9% p> 0 .05). In the poor-metabolizer group (*2/*2 or *2/*3), 20.1% of patients had CV events on follow up compared to 15.6% in the extensive metabolizer group (*1/*1), whereas in the intermediate group only 10% of patients had CV events (p>0.05).
Conclusion:We conclude that patients carrying CYP2C19 loss-of-function alleles had a higher rate of subsequent cardiovascular events as against those with normal allele. Lack of significant events even in presence of variant alleles justifies us to some extent to continue clopidogrel in our patients.
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