title: Familial lethal inheritance of a mutated paternal gene in females causing X-linked ornithine transcarbamylase (OTC) deficiency.
abstract: A Leu148Phe substitution of the ornithine transcarbamylase (OTC) gene was identified in a 2-year-old girl with OTC deficiency (14% of control). Her two elder sisters died in childhood of hyperammonemia, and the patient also died of OTC deficiency. Enzyme activity in Cos1 cells transfected by the mutant cDNA was undetectable, thereby indicating a definite pathogenic mutation. Familial gene analysis showed that the mother had wild-type OTC alleles on both X-chromosomes and the father was a mosaic for the mutant allele in his lymphocytes and spermatozoa. This clinical case shows that a somatic and germline mosaicism for a single-gene disorder led to an unusual pattern of X-linked inheritance in the family, and all three daughters in the family died of OTC deficiency. The possibility that inherited factors will lead to skewed X-inactivation needs to be considered.
authors.affiliation: Department of Pediatrics, Kumamoto University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Komaki
authors.forename: T
authors.initials: T
authors.lastname: Matsuura
authors.forename: K
authors.initials: K
authors.lastname: Oyanagi
authors.forename: R
authors.initials: R
authors.lastname: Hoshide
authors.forename: K
authors.initials: K
authors.lastname: Kiwaki
authors.forename: F
authors.initials: F
authors.lastname: Endo
authors.forename: M
authors.initials: M
authors.lastname: Shimadzu
authors.forename: I
authors.initials: I
authors.lastname: Matsuda
mesh_terms: D017809:Fatal Outcome; D005260:Female; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D007223:Infant; D009030:Mosaicism / Q000235:genetics*; D009954:Ornithine Carbamoyltransferase / Q000235:genetics; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014960:X Chromosome
chemical_list: D009954:Ornithine Carbamoyltransferase