title: Saethre-Chotzen syndrome: notable intrafamilial phenotypic variability in a large family with Q28X TWIST mutation.
abstract: Saethre-Chotzen syndrome is an autosomal dominant disease characterized by craniosynostosis, ptosis, and limb and external ear abnormalities. Variable expressivity is a well-known phenomenon in this disorder. A large Indian family has been recently identified as carrying a nonsense TWIST mutation (Q28 X) in 17 members, of whom 16 were examined in detail. Only 4 (25%) of the patients showed patent craniostenosis, namely, oxycephaly. The penetrance of craniosynostosis in this family is lower than previously reported in the literature. Fifteen patients (93%) had moderate to severe ptosis. Minor limb and external ear abnormalities were present in most patients. Eyelid features were the hallmark of the disease for 12 members of the family, suggesting that mutations in TWIST may lead to a phenotype with mainly palpebral features and no craniostenosis. The clinical analysis of this large family clearly illustrates the significant variable expressivity, probably related to haploinsufficiency because of the TWIST mutation. This phenotypic variability remains unclear but could be the result of modifier genes and/or genetic background effect, as noticed previously in the transgenic twist-null heterozygous mice.
authors.affiliation: LGME du CNRS, U-184 INSERM, Faculté de Médecine, Strasbourg, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.forename: Partha
authors.initials: P
authors.lastname: Biswas
authors.forename: Govindsamy
authors.initials: G
authors.lastname: Kumaramanickavel
authors.forename: Corinne
authors.initials: C
authors.lastname: Stoetzel
authors.forename: Renaud
authors.initials: R
authors.lastname: Quillet
authors.forename: Jyotirmay
authors.initials: J
authors.lastname: Biswas
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lajeunie
authors.forename: Dominique
authors.initials: D
authors.lastname: Renier
authors.forename: Fabienne
authors.initials: F
authors.lastname: Perrin-Schmitt
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics* / Q000473:pathology; D019943:Amino Acid Substitution; D000818:Animals; D005192:Family Health; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*; D051879:Twist-Related Protein 1
chemical_list: D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1