title: Paternal transmission and slow elimination of mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients.
abstract: In ten families with late-onset ornithine transcarbamylase (OTC) deficiency in male patients, three mutant alleles-R40H, R277W, and Y55D-were identified. In a total of 20 informative parent-offspring pairs, father-to-daughter transmission and mother-to-offspring transmission occurred in five (25%) and 15 (75%), respectively, indicating that paternal transmission contributes substantially to the pool of these mutant alleles. Relative reproductive fitness of males and females carrying the mutant alleles was calculated to be 0.49 and 0.89, respectively. Comparison of the life span of the mutant alleles, estimated on the basis of these fitness values with those associated with classic phenotype (neonatal onset) in which reproductive fitness of male patients was nil, revealed that mutant alleles associated with the late-onset phenotype were eliminated more slowly. This would allow the late-onset phenotype mutant alleles to be retained more frequently in a population than those associated with classic phenotype. Although heterozygous females carrying the late-onset phenotype mutant alleles were generally asymptomatic, one female carrying the R40H allele died after a hyperammonemic episode at the age of 18 years. Such heterozygous females should be alerted to possible hyperammonemic crisis.
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Numata
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Eimei
authors.initials: E
authors.lastname: Harada
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Maeno
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Ueki
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Fujii
authors.affiliation: Biostatistics Center, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yanagawa
authors.affiliation: Division of Pediatrics, Oita Prefecture Hospital, 476, Bunyo, Oita, 870-8511, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takenaka
authors.affiliation: Division of Pediatrics, Oita Prefecture Hospital, 476, Bunyo, Oita, 870-8511, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Pediatrics, Nakatsu Municipal Hospital, 173 Shimoikenaga, Nakatsu, 871-0011, Japan.
authors.forename: Shinkai
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Department of Pediatrics, Nakatsu Municipal Hospital, 173 Shimoikenaga, Nakatsu, 871-0011, Japan.
authors.forename: Terufumi
authors.initials: T
authors.lastname: Goushi
authors.affiliation: Department of Internal Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yasutake
authors.affiliation: Department of Internal Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Mizuta
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. yoshino@med.kurume-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshino
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D009954:Ornithine Carbamoyltransferase / Q000235:genetics*; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype
chemical_list: D009954:Ornithine Carbamoyltransferase