Expression of Four Mutant Human Ornithine Transcarbamylase Genes in Cultured Cos 1 Cells Relates to Clinical Phenotypes

Overview

Journal Hum Genet

Specialty Genetics

Date 1994 Feb 1

PMID 8112735

Citations 3

Authors

T Matsuura

R Hoshide

C Setoyama

S Komaki

K Kiwaki

F Endo

S Nishikawa

I Matsuda

Affiliations

Soon will be listed here.

Abstract

Ornithine transcarbamylase (OTC) deficiency is an X-linked disease with a heterogeneous phenotype, even in affected males. To detect mutations in the OTC gene using genomic DNA, we have developed a method in which all exons and adjacent introns are amplified and sequenced. Although this approach detected mutations in many cases, the relationship between a mutation and the OTC phenotype was not firmly established. Therefore, we investigated the issue by expression analysis of mutant OTC cDNA in cultured cells. Four mutant OTC cDNAs were constructed, based on the reported cases, using our newly developed method. The normal (wild-type) human OTC cDNA was reproducibly expressed at high levels in these Cos 1 cells. Predicted OTC activities of mutant OTC cDNAs ranged from 0% to 8.9% of the normal level together with variable amounts of the enzyme protein. The predicted enzyme activities account for the clinical phenotype of the disease. Our observations confirm that these mutations are responsible for OTC deficiency in these patients.

Citing Articles

Phenotypic variability in male patients carrying the mutant ornithine transcarbamylase (OTC) allele, Arg40His, ranging from a child with an unfavourable prognosis to an asymptomatic older adult.

Matsuda I, Matsuura T, Nishiyori A, Komaki S, Hoshide R, Matsumoto T J Med Genet. 1996; 33(8):645-8.

PMID: 8863155 PMC: 1050697. DOI: 10.1136/jmg.33.8.645.

Molecular basis of phenotypic variation in patients with argininemia.

Uchino T, Snyderman S, Lambert M, Qureshi I, Shapira S, Sansaricq C Hum Genet. 1995; 96(3):255-60.

PMID: 7649538 DOI: 10.1007/BF00210403.

Identification of two new aberrant splicings in the ornithine carbamoyltransferase (OCT) gene in two patients with early and late onset OCT deficiency.

Matsuura T, Hoshide R, Komaki S, Kiwaki K, Endo F, Nakamura S J Inherit Metab Dis. 1995; 18(3):273-82.

PMID: 7474892 DOI: 10.1007/BF00710415.

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