Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency
Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency
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DOI：
10.1093/hmg/8.4.655
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发表时间：
1999-04-01
影响因子：
3.5
通讯作者：
Hjelm, NM
中科院分区：
文献类型：
--
作者：
Tang, NLS;Ganapathy, V;Hjelm, NM
系统性原发性肉碱缺乏症（CDSP，OMIM 212140）是一种常染色体隐性遗传疾病，其特征是血清和细胞内肉碱浓度低，CDSP 可能在出生后 2 年内出现类似雷氏综合征的急性代谢紊乱。 3 岁后，CDSP 患者可能出现心肌病和肌无力。据报道，在一个家族中与 5q 中的 D5S436 存在连锁，最近克隆的有机阳离子转运蛋白 OCTN2 的同源物（具有钠依赖性肉碱摄取特性）也被映射到相同的基因座。我们在已确认的 CDSP 家族中筛选了 OCTN2 突变。 OCTN2 的一个截短突变 (Trp132Stop) 和一个错义突变 (Pro478Leu) 与两个沉默多态性一起被鉴定，突变体 cDNA 的表达表明这两种突变几乎没有摄取活性！我们的数据表明 OCTN2 的突变是导致 CDSP 的原因。鉴定这种疾病的潜在基因将有助于快速检测携带者并对受影响的患者进行产后诊断。
Systemic primary carnitine deficiency (CDSP, OMIM 212140) is an autosomal recessive disease characterized by low serum and intracellular concentrations of carnitine, CDSP may present with acute metabolic derangement simulating Reye's syndrome within the first 2 years of life. After 3 years of age, patients with CDSP may present with cardiomyopathy and muscle weakness. A linkage with D5S436 in 5q was reported in a family, A recently cloned homologue of the organic cation transporter, OCTN2, which has sodium-dependent carnitine uptake properties, was also mapped to the same locus. We screened for mutation in OCTN2 in a confirmed CDSP family. One truncating mutation (Trp132Stop) and one missense mutation (Pro478Leu) of OCTN2 were identified together with two silent polymorphisms, Expression of the mutant cDNAs revealed virtually no uptake activity for both mutation!;. Our data indicate that mutations in OCTN2 are responsible for CDSP. Identification of the underlying gene in this disease will allow rapid detection of carriers and postnatal diagnosis of affected patients.