title: Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation.
abstract: Nance-Horan syndrome (NHS) is an X-linked disorder characterized by congenital cataracts, dental anomalies, dysmorphic features, and, in some cases, mental retardation. NHS has been mapped to a 1.3-Mb interval on Xp22.13. We have confirmed the same localization in the original, extended Australian family with NHS and have identified protein-truncating mutations in a novel gene, which we have called "NHS," in five families. The NHS gene encompasses approximately 650 kb of genomic DNA, coding for a 1,630-amino acid putative nuclear protein. NHS orthologs were found in other vertebrates, but no sequence similarity to known genes was identified. The murine developmental expression profile of the NHS gene was studied using in situ hybridization and a mouse line containing a lacZ reporter-gene insertion in the Nhs locus. We found a complex pattern of temporally and spatially regulated expression, which, together with the pleiotropic features of NHS, suggests that this gene has key functions in the regulation of eye, tooth, brain, and craniofacial development.
authors.affiliation: Menzies Centre for Population Health Research, University of Tasmania, Hobart, Australia.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.forename: James D
authors.initials: JD
authors.lastname: McKay
authors.forename: Michèle M
authors.initials: MM
authors.lastname: Sale
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Russell-Eggitt
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: M Gabriela
authors.initials: MG
authors.lastname: Wirth
authors.forename: James E
authors.initials: JE
authors.lastname: Elder
authors.forename: Alan
authors.initials: A
authors.lastname: Nicoll
authors.forename: Michael P
authors.initials: MP
authors.lastname: Clarke
authors.forename: Liesel M
authors.initials: LM
authors.lastname: FitzGerald
authors.forename: James M
authors.initials: JM
authors.lastname: Stankovich
authors.forename: Marie A
authors.initials: MA
authors.lastname: Shaw
authors.forename: Shiwani
authors.initials: S
authors.lastname: Sharma
authors.forename: Srecko
authors.initials: S
authors.lastname: Gajovic
authors.forename: Peter
authors.initials: P
authors.lastname: Gruss
authors.forename: Shelley
authors.initials: S
authors.lastname: Ross
authors.forename: Paul
authors.initials: P
authors.lastname: Thomas
authors.forename: Anne K
authors.initials: AK
authors.lastname: Voss
authors.forename: Tim
authors.initials: T
authors.lastname: Thomas
authors.forename: Jozef
authors.initials: J
authors.lastname: Gécz
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001315:Australia; D002386:Cataract / Q000151:congenital / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D008607:Intellectual Disability / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013577:Syndrome; D014071:Tooth Abnormalities / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C488621:NHS protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger