BACKGROUND: H syndrome is a rare autosomal recessive genetic disorder which involves the skin and other systemic organs and is caused by mutations in the SLC29A3 gene. OBJECTIVES: To disclose the molecular basis of H syndrome in two Syrian families, and to determine the localization of hENT3 in human skin. METHODS: DNA from two Syrian families with H syndrome was analyzed through direct sequencing, and the expression of hENT3 in normal human skin was investigated by in situ hybridization and immunostaining. RESULTS: We identified two novel mutations in the SLC29A3 gene: a homozygous splice site mutation IVS1+2T>G predicted to cause a splicing error, and a homozygous missense mutation c.1157G>A (p.R386Q) which substituted highly conserved amino acid residue in a transmembrane domain of hENT3. Furthermore, we demonstrate that hENT3 is expressed in histiocytes as well as in endothelium of blood and lymphatic vessels in normal human skin. CONCLUSIONS: Our results further enhance the mutation spectrum of the SLC29A3 gene for this rare genetic disorder, and also suggest potential pathomechanisms for the skin lesions resulting from SLC29A3 mutations.
BACKGROUND:H syndrome is a rare autosomal recessive genetic disorder which involves the skin and other systemic organs and is caused by mutations in the SLC29A3 gene. OBJECTIVES: To disclose the molecular basis of H syndrome in two Syrian families, and to determine the localization of hENT3 in human skin. METHODS: DNA from two Syrian families with H syndrome was analyzed through direct sequencing, and the expression of hENT3 in normal human skin was investigated by in situ hybridization and immunostaining. RESULTS: We identified two novel mutations in the SLC29A3 gene: a homozygous splice site mutation IVS1+2T>G predicted to cause a splicing error, and a homozygous missense mutation c.1157G>A (p.R386Q) which substituted highly conserved amino acid residue in a transmembrane domain of hENT3. Furthermore, we demonstrate that hENT3 is expressed in histiocytes as well as in endothelium of blood and lymphatic vessels in normal human skin. CONCLUSIONS: Our results further enhance the mutation spectrum of the SLC29A3 gene for this rare genetic disorder, and also suggest potential pathomechanisms for the skin lesions resulting from SLC29A3 mutations.
Authors: Philippe M Campeau; James T Lu; Gautam Sule; Ming-Ming Jiang; Yangjin Bae; Simran Madan; Wolfgang Högler; Nicholas J Shaw; Steven Mumm; Richard A Gibbs; Michael P Whyte; Brendan H Lee Journal: Hum Mol Genet Date: 2012-08-08 Impact factor: 6.150