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We identified nine individuals from three unrelated Turkish families with a unique autosomal recessive syndrome characterized by type I microtia, microdontia, and profound congenital deafness associated with a complete absence of inner ear structures (Michel aplasia). We later demonstrated three different homozygous mutations (p.S156P, p.R104X, and p.V206SfsX117) in the fibroblast growth factor 3 (FGF3) gene in affected members of these families, cosegregating with the autosomal recessive transmission as a completely penetrant phenotype. These findings demonstrate the involvement of FGF3 mutations in a human malformation syndrome for the first time and contribute to our understanding of the role this gene plays in embryonic development. Of particular interest is that the development of the inner ear is completely disturbed at a very early stage--or the otic vesicle is not induced at all--in all of the affected individuals who carried two mutant FGF3 alleles.

Background and Aim: Recent studies have revealed a genotype-phenotype correlation for mutations in the GJB2 gene. Since ethnic difference may have an effect for the degree of hearing loss due to background genes, we aimed to search for confirmation of previously suggested genotype-phenotype correlation in GJB2 deafness in the Turkish population., Methods: Pure tone audiograms of 63 unrelated probands with GJB2-associated hearing loss having 15 different mutations were obtained and evaluated for correlation between the degree of hearing loss and genotypes., Results: Three GJB2 genotypes identified in more than one family were homozygous c.35delG (44 probands), homozygous p.E120del (four probands) and c.[35delG]+[IVS1+1G>A] (two probands). No statistical difference for the degree of hearing loss was observed when the genotypes were compared individually or grouped according to their effects on the protein. The most likely explanation for this result is the relatively small size of the studied population. Degree of hearing loss was variable in c.35delG and p.E120del homozygotes. Intra-familial phenotypic variability was present for some genotypes. The detailed audiological data for homozygous p.E120del and c.[35delG]+[328delG] genotypes are reported for the first time in this study., Conclusion: Previously reported genotype-phenotype correlations for the GJB2 deafness should be cautiously interpreted during the clinical counseling since variability in the degree of hearing loss is present for all GJB2 genotypes.