TY - JOUR
T1 - Mutations in the Fatty Acid 2-Hydroxylase Gene Are Associated with Leukodystrophy with Spastic Paraparesis and Dystonia
AU - Edvardson, Simon
AU - Hama, Hiroko
AU - Shaag, Avraham
AU - Gomori, John Moshe
AU - Berger, Itai
AU - Soffer, Dov
AU - Korman, Stanley H.
AU - Taustein, Ilana
AU - Saada, Ann
AU - Elpeleg, Orly
N1 - Funding Information:
We gratefully acknowledge the collaboration of the patients' families. This work was supported by the Joint Research Fund of the Hebrew University and Hadassah Medical Organization and by the National Institute of Health grant NS060807.
PY - 2008/11/17
Y1 - 2008/11/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=55049092207&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2008.10.010
DO - 10.1016/j.ajhg.2008.10.010
M3 - Article
AN - SCOPUS:55049092207
VL - 83
SP - 643
EP - 648
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 5
ER -