2013/08/08 by Bryn D. Webb, Tracy Brandt, L. Liu +9 · 17 citations
Medicine · Biochemistry, Genetics and Molecular Biology · #Cell Adhesion Molecules Research #Renal and related cancers #Alport syndrome #Genetics #Haplotype #Population #Founder effect #Mutation #Genetic linkage #Allele #Medicine #Biology #Glomerulonephritis #Gene #Kidney
paper · doi:10.1111/cge.12247
published in Clinical Genetics 86(2), 155-160 (Wiley)
openalex publication_date 2013/08/08 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/27
Alport syndrome is an inherited progressive nephropathy arising from mutations in the type IV collagen genes, COL4A3, COL4A4, and COL4A5. Symptoms also include sensorineural hearing loss and ocular lesions. We determined the molecular basis of Alport syndrome in a non-consanguineous Ashkenazi Jewish family with multiple affected females using linkage analysis and next generation sequencing. We identified a homozygous COL4A3 mutation, c.4063del, in affected individuals with mutant alleles inherited from each parent on partially conserved haplotypes. Large-scale population screening of 2017 unrelated Ashkenazi Jewish samples revealed a carrier frequency of 1 in 183 indicating that COL4A3 c.4063del is a founder mutation which may be a common cause of Alport syndrome in this population. Additionally, we determined that heterozygous mutation carriers in this family do not meet criteria for a diagnosis of Thin Basement Membrane Nephropathy and concluded that carriers of c.4063del are not likely to develop benign familial hematuria.