OBJECTIVE:

To report the phenotype-genotype correlation in a Belgian family that was ascertained to have a novel missense mutation in the NOG gene mapping to chromosome 17q22.

STUDY DESIGN:

To describe the phenotype, a retrospective case study was performed based on the otologic, audiologic, ophthalmologic, and radiologic data of the mutation carriers of the NOG gene.

SETTING:

Tertiary referral center.

PATIENTS:

All members of a Belgian kindred who carried the novel missense mutation in the NOG gene (NOG, Trp205Cys [W205C]; 1426G>C).

INTERVENTIONS:

Diagnostic otologic and ophthalmologic examination, audiometric analysis, and radiologic imaging.

MAIN OUTCOME MEASURES:

Phenotype-genotype correlations.

RESULTS:

All five mutation carriers had a typical facies. Bilateral proximal symphalangism and hyperopia were present in 80%. Five of 10 ears also had progressive early-onset conductive hearing loss caused by stapes ankylosis.

CONCLUSIONS:

So far, 14 independent NOG mutations have been identified. The autosomal dominant disorder described in the present family was caused by a novel NOG missense mutation (NOG, Trp205Cys [W205C]; 1426G>C). The phenotype correlated well with the facioaudiosymphalangism syndrome. The mutation carriers demonstrated progressive multiple joint fusions, hyperopia, early-onset conductive deafness, and a typical facies.