Homozygous mutation of the PHOX2B gene in congenital central hypoventilation syndrome (Ondine's Curse)

Abstract

Homozygosity for a dominant allele is relatively rare and preferentially observed in communities with high inbreeding. According to the definition of true dominance, similar phenotypes should be observed in patients heterozygous and homozygous for a dominant mutation. However, the homozygous phenotype usually tends to be more severe than the heterozygous one. In these cases, the wild-type and mutant alleles are semi-dominant. Here we report a patient with a Congenital Central Hypoventilation Syndrome (CCHS) phenotype and homozygosity for a PHOX2B gene mutation leading to an alanine expansion shorter than the threshold hitherto observed in CCHS patients with a heterozygous mutation. This observation adds the concept of mutational threshold per se to the discussion about dominant and recessive alleles.