Stapes ankylosis in a family with a novel NOG mutation: otologic features of the facioaudiosymphalangism syndrome.
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.


METHODS
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.


METHODS
Tertiary referral center.


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


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


METHODS
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.
Declau
Frank
F
Department of Oto-Rhino-Laryngology, University of Antwerp, Brugge, Belgium. frank.declau@pandora.be
Van den Ende
Jenneke
J
Baten
Emiel
E
Mattelaer
Paul
P
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000844:Ankylosis / Q000175:diagnosis / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D002886:Chromosomes, Human, Pair 17; D005128:Eye Diseases / Q000235:genetics; D005260:Female; D005838:Genotype; D006314:Hearing Loss, Conductive / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D006956:Hyperopia / Q000235:genetics; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D012189:Retrospective Studies; D013199:Stapes / Q000002:abnormalities / Q000503:physiopathology*; D013577:Syndrome; D013933:Thumb / Q000002:abnormalities; D014034:Toes / Q000002:abnormalities; D000099176:Noggin Protein
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D000099176:Noggin Protein