TY - JOUR
T1 - Mutations in a Novel Gene, NHS, Cause the Pleiotropic Effects of Nance-Horan Syndrome, Including Severe Congenital Cataract, Dental Anomalies, and Mental Retardation
AU - Burdon, Kathryn P.
AU - McKay, James D.
AU - Sale, Michèle M.
AU - Russell-Eggitt, Isabelle M.
AU - Mackey, David A.
AU - Wirth, M. Gabriela
AU - Elder, James E.
AU - Nicoll, Alan
AU - Clarke, Michael P.
AU - FitzGerald, Liesel M.
AU - Stankovich, James M.
AU - Shaw, Marie A.
AU - Sharma, Shiwani
AU - Gajovic, Srecko
AU - Gruss, Peter
AU - Ross, Shelley
AU - Thomas, Paul
AU - Voss, Anne K.
AU - Thomas, Tim
AU - Gécz, Jozef
AU - Craig, Jamie E.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - 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 ∼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.
AB - 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 ∼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.
UR - http://www.scopus.com/inward/record.url?scp=0242438883&partnerID=8YFLogxK
U2 - 10.1086/379381
DO - 10.1086/379381
M3 - Article
C2 - 14564667
AN - SCOPUS:0242438883
SN - 0002-9297
VL - 73
SP - 1120
EP - 1130
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -