Mutations in a Novel Gene, NHS, Cause the Pleiotropic Effects of Nance-Horan Syndrome, Including Severe Congenital Cataract, Dental Anomalies, and Mental Retardation

Kathryn P. Burdon, James D. McKay, Michèle M. Sale, Isabelle M. Russell-Eggitt, David A. Mackey, M. Gabriela Wirth, James E. Elder, Alan Nicoll, Michael P. Clarke, Liesel M. FitzGerald, James M. Stankovich, Marie A. Shaw, Shiwani Sharma, Srecko Gajovic, Peter Gruss, Shelley Ross, Paul Thomas, Anne K. Voss, Tim Thomas, Jozef GéczJamie E. Craig

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89 Citations (Scopus)

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 ∼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.

Original languageEnglish
Pages (from-to)1120-1130
Number of pages11
JournalAmerican Journal of Human Genetics
Volume73
Issue number5
DOIs
Publication statusPublished or Issued - Nov 2003
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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