Fine mapping of autosomal dominant nonsyndromic hearing impairment DFNA21 to chromosome 6p24.1-22.3

• Published in: American journal of medical genetics. Part A Vol. 137A; no. 1; pp. 41 - 46
• Main Authors: de Brouwer, Arjan P.M., Kunst, Hendrikus P.M., Krebsova, Alice, van Asseldonk, Karin, Reis, André, Snoeckx, Rik L., Van Camp, Guy, Cremers, Cor W.R.J., Cremers, Frans P.M., Kremer, Hannie
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-08-2005
• Subjects: Chromosome Mapping; Chromosomes, Human, Pair 6 - genetics; DFNA21; Family Health; Female; Genes, Dominant; Genetic Markers; Genetic Predisposition to Disease - genetics; hearing impairment; Hearing Loss - genetics; Hearing Loss - pathology; Humans; Lod Score; Male; Pedigree
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.30844

Previously, the DFNA21 locus was positioned telomeric to the DFNA13 locus based on testing of candidate loci. One family member in this region did not carry the at risk haplotype, although he had the same nonspecific midfrequency hearing impairment as other affected family members. Hence, we performed a whole genome linkage scan excluding other regions of the genome and confirming the localization of DFNA21 to 6p22.3‐24.1. The DFNA21 interval was determined to span 12.4 Mb (∼22 cM) and is delimited on the telomeric side by BV097155 and on the centromeric side by D6S1691. A maximum lod score of 3.51 (θ = 0.066), was calculated for marker D6S1721. The DFNA21 region does not overlap the adjacent DFNA31 and DFNA13 loci and contains 31 known genes. The coding regions and exon–intron boundaries of four candidate genes, SOX4, MYLIP, CAP2, and RPEL1, were sequenced, but no mutations were identified. © 2005 Wiley‐Liss, Inc.