Identification of Two Novel Mutations in <b><i>SLC29A3 </i></b>Encoding an Equilibrative Nucleoside Transporter (hENT3) in Two Distinct Syrian Families with H Syndrome: Expression Studies of <b><i>SLC29A3</i></b> (hENT3) in Human Skin

<b><i>Background:</i></b> H syndrome is a rare autosomal recessive genetic disorder which involves the skin and other systemic organs and is caused by mutations in the <i>SLC29A3</i> gene. <b><i>Objectives:</i></b> To disclose the molecular basis of H syndrome in two Syrian families, and to determine the localization of hENT3 in human skin. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> We identified two novel mutations in the <i>SLC29A3</i> 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. <b><i>Conclusions:</i></b> Our results further enhance the mutation spectrum of the <i>SLC29A3</i> gene for this rare genetic disorder, and also suggest potential pathomechanisms for the skin lesions resulting from <i>SLC29A3</i> mutations.