An alpha-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual non-syndromic deafness, DFNB21

In our efforts to identify new loci responsible for non-syndromic autosomalrecessive forms of deafness, DFNB loci, we have pursued the analysis oflarge consanguineous affected families living in geographically isolatedareas. Here, we report on the study of a Lebanese family comprising ninemembers presenting with a pre-lingual severe to profound sensorineuralisolated form of deafness. Linkage analysis led to the characterization ofa new locus, DFNB21, which was assigned to chromosome 11q23-25. Alreadymapped to this chromosomal region was TECTA. This gene encodesalpha-tectorin, a 2155 amino acid protein which is a component of thetectorial membrane. This gene recently has been shown to be responsible fora dominant form of deafness, DFNA8/12. Sequence analysis of the TECTA genein the DFNB21- affected family revealed a G to A transition in the donorsplice site (GT) of intron 9, predicted to lead to a truncated protein of971 amino acids. This establishes that alpha-tectorin mutations can beresponsible for both dominant and recessive forms of deafness. Comparisonof the phenotype of the DFNB21 heterozygous carriers with that ofDFNA8/12-affected individuals supports the hypothesis that the TECTAmutations which cause the dominant form of deafness have adominant-negative effect. The present results provide genetic evidence foralpha-tectorin forming homo- or heteromeric structures.