Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China.
NHC Key Laboratory of Birth Defects Research, Prevention and Treatment (Hunan Provincial Maternal and Child Health Care Hospital), Changsha, Hunan, China.
Mol Genet Genomic Med. 2019 Sep;7(9):e901. doi: 10.1002/mgg3.901. Epub 2019 Jul 30.
Primary carnitine deficiency (PCD) is an autosomal recessive disorder of carnitine transportation caused by mutations in the SLC22A5 that lead to low serum carnitine levels and decreased intracellular carnitine accumulation. Characteristic clinical findings are hypoketotic hypoglycemia and skeletal and cardiac myopathy.
To genetically diagnose 24 unrelated Chinese patients with PCD, including 18 infants and six adults.
The entire coding region and the intron-exon boundaries of SLC22A5 were amplified by polymerase chain reaction (PCR). In silico analyses and reverse transcription-polymerase chain reaction (RT-PCR) were used to predict variants' impact on protein structure and function.
Disease-causing variants in the SLC22A5 were identified in all 24 subjects, and c.288delG, c.495C>A, c.774_775insTCG, c.824+1G>A, and c.1418G>T were novel. The novel variant c.824+1G>A caused a truncated protein p.Phe276Tyrfs*8.
We identified 13 variants in the SLC22A5 in 24 PCD patients, and five of these variants are novel mutations. c.824+1G>A was confirmed to alter mRNA splicing by reverse transcription PCR. Furthermore, our findings broaden the mutation spectrum of SLC22A5 and the understanding of the diverse and variable effects of PCD variants.
原发性肉碱缺乏症（PCD）是一种常染色体隐性遗传疾病，由 SLC22A5 基因突变引起，导致血清肉碱水平降低和细胞内肉碱积累减少。其特征性临床表现为低酮性低血糖和骨骼及心肌病变。
对 24 例 PCD 患者（包括 18 例婴儿和 6 例成人）进行基因诊断。
通过聚合酶链反应（PCR）扩增 SLC22A5 的整个编码区和内含子-外显子边界。通过计算机分析和反转录-聚合酶链反应（RT-PCR）预测变异对蛋白质结构和功能的影响。
在 24 例患者中均发现 SLC22A5 中的致病变异，其中 c.288delG、c.495C>A、c.774_775insTCG、c.824+1G>A 和 c.1418G>T 为新突变。新发现的 c.824+1G>A 导致截短蛋白 p.Phe276Tyrfs*8。
我们在 24 例 PCD 患者中发现了 13 种 SLC22A5 变异，其中 5 种为新突变。c.824+1G>A 通过 RT-PCR 被确认为改变了 mRNA 剪接。此外，我们的发现拓宽了 SLC22A5 的突变谱，并加深了对 PCD 变异多样性和多变性的理解。
