Pharmaceutical Sciences Research Center, Tehran medical Sciences, Islamic Azad University, Tehran, Iran.
Department of Biology, Faculty of Basic Sciences, Semnan University, Semnan, 35131-19111, Iran.
BMC Med Genet. 2019 Aug 29;20(1):147. doi: 10.1186/s12881-019-0879-7.
The SLC29A3 gene, encoding a nucleoside transporter protein, is found in intracellular membranes. Based on the literatures, mutations in this gene cause a wide range of clinical manifestations including H syndrome, pigmented hypertrichosis with insulin dependent diabetes, Faisalabad histiocytosis, and dysosteosclerosis. However, all these disorders with their different names and terminologies are actually the same entity termed H syndrome.
We report four GJB2 and GJB6 negative deaf patients from two Iranian related families who present the associated symptoms of SLC29A3-disorder. Whole Exome Sequencing (WES) using Next Generation Illumina Sequencing was used to enrich all exons of protein-coding genes as well as some other important genomic regions in one of studied patients. A novel homozygous frame-shift mutation c.307-308delTT (p.Phe103fs) in exon 3 of SLC29A3 gene was identified in a 35 years old man with profound hearing loss, camptodactyly, rheumatoid arthritis and delayed puberty without any skin changes, short stature and insulin dependent diabetes mellitus. The mutation found was also confirmed by Sanger sequencing in other studied patients and their healthy parents. In compared to proband, however the clinical manifestations of these patients were different, indicating variable expressivity of mutant SLC29A3 gene as well as possible involvement of other modifier genes.
The present study uncovered a rare novel homozygous frame-shift mutation c.307-308delTT in SLC29A3 gene of four related patients with various manifestation of SLC29A3-disorder. Such studies can help to conduct genetic counseling and subsequently, prenatal diagnosis more accurately for individuals at the high risk of these types of genetic disorders.
SLC29A3 基因，编码一种核苷转运蛋白，位于细胞内膜上。根据文献报道，该基因的突变可导致广泛的临床表现，包括 H 综合征、色素性多毛伴胰岛素依赖型糖尿病、费萨拉巴德组织细胞增生症和骨硬化性骨发育不良。然而，所有这些具有不同名称和术语的疾病实际上都是同一种被称为 H 综合征的实体。
我们报告了来自两个伊朗相关家族的 4 名 GJB2 和 GJB6 阴性耳聋患者，他们表现出 SLC29A3 疾病的相关症状。使用下一代 Illumina 测序进行全外显子组测序 (WES)，以富集研究患者之一的所有编码蛋白基因的外显子以及其他一些重要的基因组区域。在一名 35 岁的男性中发现了 SLC29A3 基因外显子 3 中的新型纯合框移突变 c.307-308delTT(p.Phe103fs)，该患者患有严重听力损失、指掌侧弯曲、类风湿关节炎和青春期延迟，无皮肤改变、身材矮小和胰岛素依赖型糖尿病。该突变也在其他研究患者及其健康父母中通过 Sanger 测序得到证实。然而，与先证者相比，这些患者的临床表现不同，表明突变 SLC29A3 基因的表现度可变，以及可能涉及其他修饰基因。
本研究在四个具有不同 SLC29A3 疾病表现的相关患者中发现了 SLC29A3 基因罕见的新型纯合框移突变 c.307-308delTT。此类研究有助于更准确地为这些类型的遗传疾病高风险个体进行遗传咨询和随后的产前诊断。
