PHENOTYPIC VARIABILITY IN MALE-PATIENTS CARRYING THE MUTANT ORNITHINETRANSCARBAMYLASE (OTC) ALLELE, ARG40HIS, RANGING FROM A CHILD WITH ANUNFAVORABLE PROGNOSIS TO AN ASYMPTOMATIC OLDER ADULT

In five different Japanese families, we identified six male hemizygote s (aged 6, 9, 15, 17, 56, and 65 years) and a putative candidate (aged 48 years), carrying a mutant allele of the ornithine transcarbamylase (OTC) gene, a G to A substitution at nucleotide 119 in exon 2 generat ing histidine in place of arginine. OTC activity in the necropsied Liv er tissue was reduced to similar to 12% of the control and that of COS 1 cells transfected with Arg40His OTC cDNA was 10.2 +/- 1.8% of the c ontrol transfected with wild type OTC cDNA. Clinical features ranged f rom death during a hyperammonaemic attack (a 9 year old) to a 65 year old asympto matic man. We consider that the amount of protein ingested by these subjects may be one predisposing factor leading to the manif estation of this disease.