Trochet Delphine, de Pontual Loïc, Estêvao Maria Helena, Mathieu Yves, Munnich Arnold, Feingold J, Goridis Christo, Lyonnet Stanislas, Amiel Jeanne
Université Paris 5-Descartes, INSERM U-781, AP-HP, Hôpital Necker-Enfant Malades, Paris, France.
Hum Mutat. 2008 May;29(5):770. doi: 10.1002/humu.20727.
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.
显性等位基因的纯合性相对罕见，且在近亲繁殖率高的群体中更易观察到。根据真正显性的定义，对于显性突变，杂合子和纯合子患者应表现出相似的表型。然而，纯合子表型通常比杂合子表型更严重。在这些情况下，野生型和突变等位基因是半显性的。在此，我们报告一名患有先天性中枢性低通气综合征（CCHS）表型的患者，其PHOX2B基因突变呈纯合性，导致丙氨酸扩展短于迄今在杂合突变的CCHS患者中观察到的阈值。这一观察结果将突变阈值本身的概念引入了关于显性和隐性等位基因的讨论中。
