Nonsyndromic sensorineural deafness associated with the A1555G mutation in the mitochondrial small subunit ribosomal RNA in a Balinese family.

Sensorineural deafness associated with increased sensitivity to aminoglycoside antibiotics as the consequence of an A1555G mutation in the mitochondrial DNA (mtDNA) in a highly conserved region of the small (12S) rRNA gene has been reported in Caucasian, Chinese, and Japanese individuals. We report here a large family of Balinese Indonesian origin with progressive/congenital sensorineural deafness who carry the A1555G mutation. The pedigree shows a generally maternal inheritance pattern with some exceptions, which is the result of an unusual multiple entry of the mutation into the pedigree.

Genetic mapping refines DFNB3 to 17p11.2, suggests multiple alleles of DFNB3, and supports homology to the mouse model shaker-2.

The nonsyndromic congenital recessive deafness gene, DFNB3, first identified in Bengkala, Bali, was mapped to a approximately 12-cM interval on chromosome 17. New short tandem repeats (STRs) and additional DNA samples were used to identify recombinants that constrain the DFNB3 interval to less, similar6 cM on 17p11.2.

Congenital non-syndromal autosomal recessive deafness in Bengkala, an isolated Balinese village.

Bengkala is an Indonesian village located on the north shore of Bali that has existed for over 700 years. Currently, 2.2% of the 2185 people in this village have profound congenital deafness.

Analysis of short tandem repeat (STR) allele frequency distributions in a Balinese population.

Genotypes for 53 short tandem repeat (STR) markers distributed at an average of 39 cM intervals throughout the genome were determined for 46 individuals from the village of Bengkala, Bali. This village of approximately 2200 individuals has an oral and written tradition suggesting genetic bottlenecks. The allele frequency distributions in Bengkala were compared with distributions obtained by typing individuals in the CEPH data base using a Kolmogorov-Smirnov two sample test.

A gene for congenital, recessive deafness DFNB3 maps to the pericentromeric region of chromosome 17.

Two percent of the residents of Bengkala, Bali, have profound, congenital, neurosensory, nonsyndromal deafness due to an autosomal recessive mutation at the DFNB3 locus. We have employed a direct genome-wide disequilibrium search strategy, allele-frequency-dependent homozygosity mapping (AHM), and an analysis of historical recombinants to map DFNB3 and position the locus relative to flanking markers. DFNB3 maps to chromosome 17, closest to D17S261, pRM7-GT and D17S805.