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 autosomal recessive forms of deafness, DFNB loci, we have pursued the analysis of la rge consanguineous affected families living in geographically isolated area s, Here, we report on the study of a Lebanese family comprising nine member s presenting with a pre-lingual severe to profound sensorineural isolated f orm of deafness. Linkage analysis led to the characterization of a new locu s, DFNB21, which was assigned to chromosome 11q23-25, Already mapped to thi s chromosomal region was TECTA, This gene encodes alpha-tectorin, a 2155 am ino acid protein which is a component of the tectorial membrane. This gene recently has been shown to be responsible for a dominant form of deafness, DFNA8/12, Sequence analysis of the TECTA gene in the DFNB21-affected family revealed a G to A transition in the donor splice site (GT) of intron 9, pr edicted to lead to a truncated protein of 971 amino acids, This establishes that alpha-tectorin mutations can be responsible for both dominant and rec essive forms of deafness. Comparison of the phenotype of the DFNB21 heteroz ygous carriers with that of DFNA8/12-affected individuals supports the hypo thesis that the TECTA mutations which cause the dominant form of deafness h ave a dominant-negative effect. The present results provide genetic evidenc e for alpha-tectorin forming homo- or heteromeric structures.