Wang Y, Taroni F, Garavaglia B, Longo N
Division of Medical Genetics, Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
Hum Mutat. 2000 Nov;16(5):401-7. doi: 10.1002/1098-1004(200011)16:5<401::AID-HUMU4>3.0.CO;2-J.
Primary carnitine deficiency is an autosomal recessive disorder of fatty acid oxidation caused by defective carnitine transport. This disease is caused by mutations in the novel organic cation transporter OCTN2 (SLC22A5 gene). The disease can present early in life with hypoketotic hypoglycemia or later in life with skeletal myopathy or cardiomyopathy. To determine whether the variation in phenotypic severity is due to mutations retaining residual function, we extended mutational analysis of OCTN2 to four additional European families with primary carnitine deficiency. Three patients were homozygous for novel missense mutations (R169W, G242V, A301D). The fourth patient was compound heterozygous for R169W and W351R substitutions. Stable expression of all the mutations in CHO cells confirmed that all mutations abolished carnitine transport, with the exception of the A301D mutation in which residual carnitine transport was 2-3% of the value measured in cells expressing the normal OCTN2 cDNA. Analysis of the patients characterized in molecular detail by our laboratory failed to indicate a correlation between residual carnitine transport and severity of the phenotype or age at presentation.
原发性肉碱缺乏症是一种由肉碱转运缺陷引起的常染色体隐性脂肪酸氧化障碍疾病。该疾病由新型有机阳离子转运体OCTN2（SLC22A5基因）突变所致。该病在生命早期可表现为低酮性低血糖，或在生命后期表现为骨骼肌病或心肌病。为了确定表型严重程度的差异是否归因于保留残余功能的突变，我们将OCTN2的突变分析扩展至另外四个患有原发性肉碱缺乏症的欧洲家族。三名患者为新型错义突变（R169W、G242V、A301D）的纯合子。第四名患者为R169W和W351R替代的复合杂合子。在CHO细胞中所有突变的稳定表达证实，除A301D突变外，所有突变均消除了肉碱转运，在A301D突变中，残余肉碱转运为表达正常OCTN2 cDNA的细胞中所测值的2 - 3%。对我们实验室进行详细分子特征分析的患者的分析未能表明残余肉碱转运与表型严重程度或发病年龄之间存在相关性。
