Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Dermatology. 2012;224(3):277-84. doi: 10.1159/000338886. Epub 2012 May 31.
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.
To disclose the molecular basis of H syndrome in two Syrian families, and to determine the localization of hENT3 in human skin.
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.
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.
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.
H 综合征是一种罕见的常染色体隐性遗传疾病，涉及皮肤和其他全身器官，由 SLC29A3 基因突变引起。
揭示两个叙利亚家庭 H 综合征的分子基础，并确定 hENT3 在人皮肤中的定位。
通过直接测序分析来自两个 H 综合征叙利亚家庭的 DNA，并通过原位杂交和免疫染色研究 hENT3 在正常人类皮肤中的表达。
我们在 SLC29A3 基因中发现了两个新的突变：一个纯合剪接位点突变 IVS1+2T>G，预计会导致剪接错误，以及一个纯合错义突变 c.1157G>A（p.R386Q），取代了 hENT3 跨膜域中高度保守的氨基酸残基。此外，我们证明 hENT3 在正常人类皮肤的组织细胞以及血液和淋巴管内皮中表达。
我们的结果进一步增强了 SLC29A3 基因对于这种罕见遗传疾病的突变谱，并提示 SLC29A3 基因突变导致皮肤损伤的潜在发病机制。
