A spectrum of novel NPHS1 and NPHS2 gene mutations in pediatric nephrotic syndrome patients from Pakistan.
Journal - Gene (Netherlands )
Mutations in the NPHS1 and NPHS2 genes are among the main causes of early-onset and familial steroid resistant nephrotic syndrome respectively. This study was carried out to assess the frequencies of mutations in these two genes in a cohort of Pakistani pediatric NS patients.Mutation analysis was carried out by direct sequencing of the NPHS1 and NPHS2 genes in 145 nephrotic syndrome (NS) patients. This cohort included 36 samples of congenital or infantile onset NS cases and 39 samples of familial cases obtained from 30 families.A total of 7 homozygous (6 novel) mutations were found in the NPHS1 gene and 4 homozygous mutations in the NPHS2 gene. All mutations in the NPHS1 gene were found in the early onset cases. Of these, one patient has a family history of NS. Homozygous p.R229Q mutation in the NPHS2 gene was found in two children with childhood-onset NS.Our results show a low prevalence of disease causing mutations in the NPHS1 (22% early onset, 5.5% overall) and NPHS2 (3.3% early onset and 3.4% overall) genes in the Pakistani NS children as compared to the European populations. In contrast to the high frequency of the NPHS2 gene mutations reported for familial SRNS in Europe, no mutation was found in the familial Pakistani cases. To our knowledge, this is the first comprehensive screening of the NPHS1 and NPHS2 gene mutations in sporadic and familial NS cases from South Asia.Copyright © 2012 Elsevier B.V. All rights reserved.
|ISSN : ||1879-0038|
|Mesh Heading : ||Adolescent Child Child, Preschool Cohort Studies DNA Mutational Analysis Female Homozygote Humans Infant Infant, Newborn Intracellular Signaling Peptides and Proteins Male Membrane Proteins Nephrotic Syndrome methods|
|Mesh Heading Relevant : ||Mutation genetics genetics genetics|
Genetic heterogeneity for autosomal dominant familial hypertrophic cardiomyopathy in a Pakistani family.
Journal - Journal of the College of Physicians and Surgeons--Pakistan : JCPSP (Pakistan )
To identify the gene causing inherited hypertrophic cardiomyopathy (HCM) in a Pakistani family.Cross-sectional, observational study.Department of Cardiology, Shifa International Hospital and Biomedical and Genetic Engineering Laboratories, Islamabad, from 2005 to 2007.A large family of 17 individuals was included in this study. In the family 6 members were suffering from hypertrophic cardiomyopathy. Linkage analysis was carried out to map the disease-causing gene. Genomic DNA from each individual of the whole family was genotyped for microsatellite markers for all the known HCM loci followed by a whole genome search. Automated DNA sequencing was done for mutation identification in the candidate genes.Linkage analysis of 17 family members showed a maximum two point Lod score of 3.97 with marker D1S1660 at chromosome 1q 32.2. A disease region of 4.16cM was defined by proximal and distal cross-overs with markers GATA135F02 and D1S3715 respectively. This region contained the candidate genes TNNT2 (cardiac troponin T) and TNNI1 (troponin I 1). Direct sequencing of these genes for the whole family containing 17 members showed no diseaseassociated mutation in either of these genes.Through linkage analysis, a disease locus for HCM family was mapped within a region of 4.16cM at chromosome 1q31.3-q32.1. So far no disease-associated mutation has been found in the candidate genes.
|ISSN : ||1022-386X|
|Mesh Heading : ||Cardiomyopathy, Hypertrophic, Familial Chromosomes, Human, Pair 1 Genetic Linkage Humans Microsatellite Repeats Mutation Pedigree Sequence Analysis, DNA Troponin I Troponin T genetics genetics|
|Mesh Heading Relevant : ||Genetic Heterogeneity genetics genetics|