Molecular characterization of a 12q22-q24 deletion associated with congenital deafness: confirmation and refinement of the DFNA25 locus.
The DFNA25 locus for autosomal dominant nonsyndromic hereditary hearing loss has been mapped to 12q21-q24 by linkage analysis. A de novo deletion in a six-year-old boy with congenital hearing loss as well as mental and motor retardation now provides independent confirmation of this genetic localization and narrows the critical interval to 13 cM in the 12q22-q24.1 region. Mapping of the deletion was performed using fluorescence in situ hybridization (FISH) analysis with region-specific yeast artificial chromosome (YAC) clones. Ten YACs 929_e_4, 959_c_3, 746_h_7, 817_h_10, 886_a_6, 916_h_9, 969_c_12, 747_e_2, 812_h_12, and 959_f_8 were absent from one chromosome 12 from the patient. Molecular analyses of eight polymorphic markers helped to narrow down the breakpoints and demonstrated that the derivative chromosome 12 is of paternal origin. Several known genes including ATP2A2, UBE3B, and VR-OAC that map in the 12q22-q24.1 region are included in the deletion. These results provide evidence that haploinsufficiency for a gene or genes in 12q22-q24.1 is associated with autosomal dominant deafness.
Petek
Erwin
E
Institute of Medical Biology and Human Genetics, Karl-Franzens University of Graz, Graz, Austria. petek@kfunigraz.ac.at
Windpassinger
Christian
C
Mach
Monika
M
Rauter
Ludwig
L
Scherer
Stephen W
SW
Wagner
Klaus
K
Kroisel
Peter M
PM
D002648:Child; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002874:Chromosome Mapping / Q000379:methods; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D005192:Family Health; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005838:Genotype; D034381:Hearing Loss / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree