Two CPT2 mutations in three Japanese patients with carnitine palmitoyltransferase II deficiency: Functional analysis and association with polymorphic haplotypes and two clinical phenotypes

Kaoru Wataya, Jun Akanuma, Patrizia Cavadini, Yoko Aoki, Shigeo Kure, Federica Invernizzi, Ichiro Yoshida, Jun Ichi Kira, Franco Taroni, Yoichi Matsubara, Kuniaki Narisawa

研究成果: ジャーナルへの寄稿学術論文査読

51 被引用数 (Scopus)

抄録

Carnitine palmitoyltransferase II (CPT II) deficiency manifests as two different clinical phenotypes: a muscular form and a hepatic form. We have investigated three nonconsanguineous Japanese patients with CPT II deficiency. Molecular analysis revealed two missense mutations, a glutamate (174)to-lysine substitution (E174K) and a phenylalanine (383)-to-tyrosine substitution (F383Y) in the CPT II cDNA. Transfection experiments in COS-1 cells demonstrated that the two mutations markedly decreased the catalytic activity of mutant CPT II. Case 1 (hepatic form) was homozygous for the F383Y mutation, whereas case 3 (muscular form) was homozygous for the E174K mutation. Case 2 and her brother, who were compound heterozygotes for E174K and F383Y, exhibited the hepatic phenotype. We also identified a novel polymorphism in the CPT2 gene, a phenylalanine (352)-tocysteine substitution (F352C), which did not alter CPT II activity in transfected cells. It was present in 21 out of 100 normal alleles in the Japanese population, but absent in Caucasian populations. Genotyping with the F352C polymorphism and the two previously reported polymorphisms, V368I and M647V, allowed normal Japanese alleles to be classified into five haplotypes. In all three families with CPT II deficiency, the E174K mutation resided only on the F1V1M1 allele, whereas the F383Y mutation was observed on the F2V2M1 allele, suggesting a single origin for each mutation.

本文言語英語
ページ(範囲)377-386
ページ数10
ジャーナルHuman Mutation
11
5
DOI
出版ステータス出版済み - 1998

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