Mutations in the Fatty Acid 2-Hydroxylase Gene Are Associated with Leukodystrophy with Spastic Paraparesis and Dystonia

Simon Edvardson, Hiroko Hama, Avraham Shaag, John Moshe Gomori, Itai Berger, Dov Soffer, Stanley H. Korman, Ilana Taustein, Ann Saada, Orly Elpeleg

Research output: Contribution to journalArticlepeer-review

154 Scopus citations

Abstract

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 of myelin 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.

Original languageEnglish
Pages (from-to)643-648
Number of pages6
JournalAmerican Journal of Human Genetics
Volume83
Issue number5
DOIs
StatePublished - 17 Nov 2008
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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