Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation.
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.
Burdon
Kathryn P
KP
Menzies Centre for Population Health Research, University of Tasmania, Hobart, Australia.
McKay
James D
JD
Sale
Michèle M
MM
Russell-Eggitt
Isabelle M
IM
Mackey
David A
DA
Wirth
M Gabriela
MG
Elder
James E
JE
Nicoll
Alan
A
Clarke
Michael P
MP
FitzGerald
Liesel M
LM
Stankovich
James M
JM
Shaw
Marie A
MA
Sharma
Shiwani
S
Gajovic
Srecko
S
Gruss
Peter
P
Ross
Shelley
S
Thomas
Paul
P
Voss
Anne K
AK
Thomas
Tim
T
Gécz
Jozef
J
Craig
Jamie E
JE
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*
D008565:Membrane Proteins; C488621:NHS protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger