Human Molecular Genetics, Vol 8, 655-660, Copyright © 1999 by Oxford University Press
NL Tang, V Ganapathy, X Wu, J Hui, P Seth, PM Yuen, RJ Wanders, TF Fok and NM Hjelm
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
mutations. 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.
ARTICLES
Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency [published erratum appears in Hum Mol Genet 1999 May;8(5):943]
Department of Chemical Pathology and Department of Paediatrics, Prince of Wales Hospital, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, People's Republic of China. nelsontang@cuhk.edu.hk
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