title: The first missense mutation of NHS gene in a Tunisian family with clinical features of NHS syndrome including cardiac anomaly.
abstract: Nance-Horan Syndrome (NHS) or X-linked cataract-dental syndrome is a disease of unknown gene action mechanism, characterized by congenital cataract, dental anomalies, dysmorphic features and, in some cases, mental retardation. We performed linkage analysis in a Tunisian family with NHS in which affected males and obligate carrier female share a common haplotype in the Xp22.32-p11.21 region that contains the NHS gene. Direct sequencing of NHS coding exons and flanking intronic sequences allowed us to identify the first missense mutation (P551S) and a reported SNP-polymorphism (L1319F) in exon 6, a reported UTR-SNP (c.7422 C>T) and a novel one (c.8239 T>A) in exon 8. Both variations P551S and c.8239 T>A segregate with NHS phenotype in this family. Although truncations, frame-shift and copy number variants have been reported in this gene, no missense mutations have been found to segregate previously. This is the first report of a missense NHS mutation causing NHS phenotype (including cardiac defects). We hypothesize also that the non-reported UTR-SNP of the exon 8 (3'-UTR) is specific to the Tunisian population.
authors.affiliation: Faculté de Médecine de Tunis, Laboratoire de Génétique Humaine, Tunis, Tunisia.
authors.forename: Manèl
authors.initials: M
authors.lastname: Chograni
authors.forename: Imen
authors.initials: I
authors.lastname: Rejeb
authors.forename: Lamia Ben
authors.initials: LB
authors.lastname: Jemaa
authors.forename: Myriam
authors.initials: M
authors.lastname: Châabouni
authors.forename: Habiba Chaabouni
authors.initials: HC
authors.lastname: Bouhamed
mesh_terms: D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000503:physiopathology; D006330:Heart Defects, Congenital / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D014071:Tooth Abnormalities / Q000235:genetics* / Q000503:physiopathology; D014416:Tunisia
chemical_list: D020413:3' Untranslated Regions; D008565:Membrane Proteins; C488621:NHS protein, human; D009687:Nuclear Proteins