Mutations in the Fatty Acid 2-Hydroxylase Gene Are Associated with Leukodystrophy with Spastic Paraparesis and Dystonia
Mutations in the Fatty Acid 2-Hydroxylase Gene Are Associated with Leukodystrophy with Spastic Paraparesis and Dystonia
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DOI：
10.1016/j.ajhg.2008.10.010
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发表时间：
2008-11-07
影响因子：
9.8
通讯作者：
Elpeleg, Orly
中科院分区：
文献类型：
--
作者：
Edvardson, Simon;Hama, Hiroko;Elpeleg, Orly
髓鞘形成是一个复杂的、发育调节的过程，髓鞘蛋白和脂质由髓鞘神经胶质细胞协调表达。九名患有儿童期痉挛、肌张力障碍、认知功能障碍和脑室周围白质疾病的患者的纯合性图谱揭示了 FA2H 基因的失活突变。 FA2H 编码脂肪酸 2-羟化酶，可催化髓鞘半乳糖脂、半乳糖神经酰胺及其硫酸化形式硫苷脂的 2-羟基化。据我们所知，这是首次发现髓磷脂脂质成分的缺陷，并且临床表型强调了半乳糖脂的2-羟基化对于髓磷脂成熟的重要性。对于患有常染色体隐性未分类脑白质营养不良或复杂痉挛性截瘫的患者，需要对 FA2H 基因进行序列分析。
Myelination is a complex, developmentally regulated process whereby myelin proteins and lipids are coordinately expressed by myelinating glial cells. Homozygosity mapping in nine patients with childhood onset spasticity, dystonia, cognitive dysfunction, and periventricular white matter disease revealed inactivating mutations in the FA2H gene. FA2H encodes the enzyme fatty acid 2-hydroxylase that catalyzes the 2-hydroxylation of myelin galactolipids, galactosylceramide, and its sulfated form, sulfatide. To our knowledge, this is the first identified deficiency of a lipid component ofniyelin and the clinical phenotype underscores the importance of the 2-hydroxylation of galactolipids for myelin maturation. In patients with autosomal-recessive unclassified leukodystrophy or complex spastic paraparesis, sequence analysis of the FA2H gene is warranted.