title: Mutations in the NOG gene are commonly found in congenital stapes ankylosis with symphalangism, but not in otosclerosis.
abstract: Human noggin (NOG) is a responsible gene for multiple synostosis syndrome (SYNS1) and proximal symphalangism (SYM1), two conditions that are recently known to be within a wider range of clinical manifestations of stapes ankylosis with symphalangism. This study was performed to determine the range of phenotype caused by NOG mutations, using Japanese patients with various phenotypes including sporadic inherited SYM1, dominantly inherited SYM1, stapes ankylosis with broad thumb and toes (Teunissen and Cremer syndrome). In addition, 33 patients with typical otosclerosis (without symphalangism) were studied. Direct sequencing analysis disclosed three novel mutations of the NOG gene in three SYM1 families. None of the otosclerosis patients without symphalangism had NOG mutations, indicating that NOG mutations may be restrictively found within patients with various skeletal abnormalities. These results together with the literature review indicated that there are no clear genotype-phenotype correlations for NOG mutations. With regard to surgical outcome, most of the patients in these three families with NOG mutations showed remarkable air-bone gap recovery after stapes surgery. Molecular genetic testing is useful to differentiate syndromic stapes ankylosis from otosclerosis, and even mild skeletal anomalies can be a diagnostic indicator of NOG-associated disease.
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan. usami@shinshu-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Usami
authors.forename: S
authors.initials: S
authors.lastname: Abe
authors.forename: S
authors.initials: S
authors.lastname: Nishio
authors.forename: Y
authors.initials: Y
authors.lastname: Sakurai
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: T
authors.initials: T
authors.lastname: Tono
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D000844:Ankylosis / Q000235:genetics* / Q000473:pathology; D044466:Asian People / Q000235:genetics; D002348:Carpal Bones / Q000002:abnormalities; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005384:Finger Joint / Q000002:abnormalities / Q000473:pathology; D005532:Foot Deformities, Congenital; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006228:Hand Deformities, Congenital; D006314:Hearing Loss, Conductive / Q000235:genetics / Q000473:pathology; D006801:Humans; D006956:Hyperopia / Q000235:genetics* / Q000473:pathology; D007592:Joint Diseases / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010040:Otosclerosis / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013199:Stapes / Q000002:abnormalities / Q000473:pathology; D013576:Syndactyly / Q000235:genetics* / Q000473:pathology; D013580:Synostosis; D013639:Tarsal Bones / Q000002:abnormalities; D013933:Thumb / Q000002:abnormalities / Q000473:pathology; D014034:Toes / Q000002:abnormalities / Q000473:pathology; D000099176:Noggin Protein
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D000099176:Noggin Protein