A genotype-phenotype correlation for @entity3492 ( @entity3492 ) XXXX .

@entity1 @entity3492 @entity4705 @entity6363 @entity4701 @entity2319 @entity65368 @entity65364 @entity393 @entity27158
INTRODUCTION: Mutations in @entity3492 are the most common cause of @entity6363 , ranging from mild to profound. Mutation analysis of this gene is widely available as a genetic diagnostic test. OBJECTIVE: To assess a possible genotype-phenotype correlation for @entity3492 . DESIGN: Retrospective analysis of audiometric data from @entity1 with @entity393 , segregating two @entity3492 mutations. SUBJECTS: Two hundred and seventy seven unrelated @entity1 with @entity393 who were seen at the ENT departments of local and university hospitals from Italy, Belgium, Spain, and the United States, and who harboured bi-allelic @entity3492 mutations. RESULTS: We found that @entity4701 homozygotes have significantly more @entity393 , compared with @entity4701 /non @entity65364 compound heterozygotes. @entity1 with two non @entity65364 mutations have even less @entity393 . We observed a similar gradient of @entity393 when we categorised mutations as inactivating (that is, stop mutations or frame shifts) or non-inactivating (that is, missense mutations). We demonstrated that certain mutation combinations (including the combination of @entity4701 with the missense mutations @entity27158 , @entity4705 , or the splice-site mutation @entity65368 , and the @entity4705 / @entity4705 genotype) are associated with significantly less @entity393 compared with @entity4701 homozygous genotypes. CONCLUSIONS: This study is the first large systematic analysis indicating that the @entity3492 genotype has a major impact on the degree of @entity393 , and identifying mild genotypes. Furthermore, this study shows that it will be possible to refine this correlation and extend it to additional genotypes. These data will be useful in evaluating habilitation options for @entity1 with @entity3492 related @entity2319 .
