A Gene Responsible for a Sensorineural Nonsyndromic Recessive Deafness Maps to Chromosome 2p22-23

Abstract

The recessive mode of transmission accounts for approximately 75% of inherited non syndromic deafness cases. We have previously designed the conditions for linkage studies of this highly heterogeneous disorder [Guilford et al. (1994) Nature Genet. 6, 24-28]. Here, using a similar approach, we have studied the segregation of a gene responsible for congenital, profound and fully penetrant sensorineural deafness in a consanguineous family living in an isolated region of Lebanon. A maximum lod score of 8.03 (theta = 0.00) was detected with a new polymorphic marker, AFMa052yb5 (D2S2144). Observed recombinants and homozygosity mapping define a maximum interval of 2 cM for this gene, DFNB6, which lies between AFMb346ye5 (a new polymorphic marker) (D2S2303) and AFM254vc9 (D2S174) on chromosome 2p22-23.

A second Middle Eastern kindred with autosomal recessive non-syndromic hearing loss segregates DFNB9

“…It was previously reported that DFNB9 lies between D2S2303 and D2S174. 5 This genetic map suggests that this region is 1.08 cM, 95% confidence interval (0, 2.59 cM). Figure 2 shows a drawing of Turkey-21, the kindred segregating DFNB9.…”

“…DFNB9 was previously mapped to 2p22-23 in a consanguineous family from Lebanon. 5 Linkage was established to markers closely linked to DFNB9 in this highly consanguineous kindred from Eastern Turkey.…”

Global Genetic Analysis

“…The loci for autosomal recessive hearing loss are extremely heterogeneous and the application of homozygosity mapping to search for responsible genes represent a classic example of the method (Guilford et al, 1994;Chaib et al, 1996). In the case of the rare recessive condition of benign recurrent intrahepatic cholestasis, common ancestry was inferred in four afflicted individuals from an isolated Dutch village (Houwen et al, 1994).…”

A sensorineural progressive autosomal recessive form of isolated deafness, DFNB13, maps to chromosome 7q34-q36

“…We have concentrated our search to identify genes responsible for autosomal recessive deafness, by analysing affected families living in isolated villages, on different countries around the Mediterranean Sea, particularly Lebanon. 6,7 In order to identify the target or defective DFNB loci present in the Lebanese population, we have collected blood samples from large affected families from different communities. We report here on the identification of a new locus, DFNB13, in a family belonging to the Christian Maronite faith.…”