Lin Yiming, Lin Weihua, Yu Ke, Zheng Faming, Zheng Zhenzhu, Fu Qingliu
Neonatal Disease Screening Center in Quanzhou, Quanzhou Women's and Children's Hospital, Quanzhou, Fujian 362000, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2017 Feb 10;34(1):35-39. doi: 10.3760/cma.j.issn.1003-9406.2017.01.008.
To investigate the mutations of SLC22A5 gene in patients with systemic primary carnitine deficiency (CDSP).
High liquid chromatography tandem mass spectrometry (HPLC/MS/MS) was applied to screen congenital genetic metabolic disease and eight patients with CDSP were diagnosed among 77 511 samples. The SLC22A5 gene mutation was detected using massarray technology and sanger sequencing. Using SIFT and PolyPhen-2 to predict the function of protein for novel variations.
Total detection rate of gene mutation is 100% in the eight patients with CDSP. Seven patients had compound heterozygous mutations and one patient had homozygous mutations. Six different mutations were identified, including one nonsense mutation [c.760C>T(p.R254X)] and five missense mutations[c.51C>G(p.F17L), c.250T>A(p.Y84N), c.1195C>T(p.R399W), c.1196G>A(p.R399Q), c.1400C>G(p.S467C)]. The c.250T>A(p.Y84N) was a novel variation, the novel variation was predicted to have affected protein structure and function. The c.760C>T (p.R254X)was the most frequently seen mutation, which was followed by the c.1400C>G(p.S467C).
This study confirmed the diagnosis of eight patients with CDSP on the gene level. Six mutations were found in the SLC22A5 gene, including one novel mutation which expanded the mutational spectrum of the SLC22A5 gene.
研究系统性原发性肉碱缺乏症（CDSP）患者中SLC22A5基因的突变情况。
应用高效液相色谱串联质谱法（HPLC/MS/MS）筛查先天性遗传代谢病，在77511份样本中确诊8例CDSP患者。采用飞行时间质谱技术和桑格测序法检测SLC22A5基因突变。使用SIFT和PolyPhen-2预测新变异对蛋白质功能的影响。
8例CDSP患者的基因突变总检出率为100%。7例患者为复合杂合突变，1例患者为纯合突变。共鉴定出6种不同的突变，包括1种无义突变[c.760C>T(p.R254X)]和5种错义突变[c.51C>G(p.F17L)、c.250T>A(p.Y84N)、c.1195C>T(p.R399W)、c.1196G>A(p.R399Q)、c.1400C>G(p.S467C)]。c.250T>A(p.Y84N)为新变异，预测该新变异会影响蛋白质结构和功能。c.760C>T(p.R254X)是最常见的突变，其次是c.1400C>G(p.S467C)。
本研究在基因水平上确诊了8例CDSP患者。在SLC22A5基因中发现了6种突变，其中包括1种新突变，扩大了SLC22A5基因的突变谱。
