The first missense mutation of NHS gene in a Tunisian family with clinical features of NHS syndrome including cardiac anomaly

Eur J Hum Genet. 2011 Aug;19(8):851-6. doi: 10.1038/ejhg.2011.52. Epub 2011 May 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Amino Acid Sequence
  • Cataract / congenital*
  • Cataract / genetics
  • Cataract / physiopathology
  • DNA Mutational Analysis
  • Exons
  • Female
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / physiopathology
  • Heart Defects, Congenital / genetics
  • Humans
  • Male
  • Membrane Proteins
  • Molecular Sequence Data
  • Mutation, Missense
  • Nuclear Proteins / genetics*
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Tooth Abnormalities / genetics*
  • Tooth Abnormalities / physiopathology
  • Tunisia

Substances

  • 3' Untranslated Regions
  • Membrane Proteins
  • NHS protein, human
  • Nuclear Proteins

Supplementary concepts

  • Nance-Horan syndrome