A probable sex difference in mutation rates in ornithine transcarbamylase deficiency

Hum Genet. 1990 Jan;84(2):163-6. doi: 10.1007/BF00208933.

Abstract

Ornithine transcarbamylase deficiency is an X-linked disease with possible manifestations in heterozygous females. Using segregation analysis in families from the literature pooled with a French series, the penetrance could be estimated to be 17% in heterozygous females (15% with severe and 2% with milder symptoms). Using these estimates, the proportion of sporadic cases among heterozygous females and hemizygous males could be derived. This proportion is 57% in females. In males, it depends on mutation rate values: assuming equal mutation rates in sperm and eggs, this proportion should be 40%. However, this value can be strongly rejected based on the proportion of isolated cases in male sibships. In both sets of data, segregation analysis provided no evidence for sporadic affected males, suggesting that there are virtually no mutations in eggs. The upper limit of the confidence interval, 0%-16%, can be taken as the maximum prior probability that an affected male occurs as the result of a new mutation in his mother's germ cells.

MeSH terms

  • Female
  • Gene Frequency
  • Genetic Linkage
  • Heterozygote
  • Humans
  • Male
  • Mutation*
  • Ornithine Carbamoyltransferase / genetics
  • Ornithine Carbamoyltransferase Deficiency Disease*
  • Pedigree
  • Sex Characteristics*
  • X Chromosome

Substances

  • Ornithine Carbamoyltransferase