Metabolism Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Gene. 2013 Jun 1;521(2):293-5. doi: 10.1016/j.gene.2013.03.033. Epub 2013 Mar 28.
Lysinuric protein intolerance is an autosomal recessive metabolic disorder caused by defective transport of the cationic amino acids lysine, arginine and ornithine in the epithelial cells of the basolateral membrane in the small intestine and renal tubules. Mutations in the solute carrier family 7, member 7, SLC7A7, gene cause this multisystemic disease with a variety of clinical symptoms such as hepatosplenomegaly, osteoporosis, hypotonia, developmental delay, pulmonary insufficiency or end-stage renal disease. In the present study, genomic structure of SLC7A7 in six Turkish patients with lysinuric protein intolerance was examined in order to detect disease causing mutations by denaturing high pressure liquid chromatography and direct sequencing. Four novel mutations were identified in SLC7A7: c.223insGTC, p.Val74_Ile75insVal; c.283insTGG, p.Glu94_Thr95insTrp; c.344_347delTTGC, p.Leu115LeufsX53; and c.1099insT, p.Ile367TyrfsX16. Clinical and biochemical findings were evaluated together with these molecular analyses.
赖氨酸尿蛋白不耐受症是一种常染色体隐性遗传代谢疾病,由小肠基底外侧膜和肾小管上皮细胞中阳离子氨基酸赖氨酸、精氨酸和鸟氨酸的转运缺陷引起。溶质载体家族 7 成员 7(SLC7A7)基因的突变导致了这种多系统疾病,其临床表现多样,包括肝脾肿大、骨质疏松症、低张力、发育迟缓、肺功能不全或终末期肾病。在本研究中,通过变性高效液相色谱法和直接测序检测了 6 名土耳其赖氨酸尿蛋白不耐受症患者的 SLC7A7 基因的基因组结构,以发现致病突变。在 SLC7A7 中鉴定出了 4 种新的突变:c.223insGTC,p.Val74_Ile75insVal;c.283insTGG,p.Glu94_Thr95insTrp;c.344_347delTTGC,p.Leu115LeufsX53;和 c.1099insT,p.Ile367TyrfsX16。对这些分子分析与临床和生化发现进行了评估。