A founder mutation in COL4A3 causes autosomal recessive Alport syndrome in the Ashkenazi Jewish population. (2nd September 2013)

• Record Type: Journal Article
• Authors: Webb, B.D.; Brandt, T.; Liu, L.; Jalas, C.; Liao, J.; Fedick, A.; Linderman, M.D.; Diaz, G.A.; Kornreich, R.; Trachtman, H.; Mehta, L.; Edelmann, L.
• Is Part Of: Clinical genetics. Volume 86:Number 2(2014:Aug.)
• Page Start: 155
• Page End: 160
• Publication Date: 2013-09-02
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12247
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12247-abs-0001"> <title>Abstract</title> <p id="cge12247-para-0001">Alport syndrome is an inherited progressive nephropathy arising from mutations in the type IV collagen genes, <italic>COL4A3</italic>, <italic>COL4A4</italic>, and <italic>COL4A5</italic>. 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 <italic>COL4A3</italic> mutation, c.40_63del, 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 <italic>COL4A3</italic> c.40_63del 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.40_63del are not likely to develop benign familial hematuria.</p> </abstract>