Salt-Losing 21-Hydroxylase Deficiency Caused by Double Homozygosity for Two "mild" Mutations


Abstract:

Context: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency presents with different severities that correlate with the genotype. The salt-losing phenotype requires 2 alleles with "severe"mutations. Case Description: We present a case of salt-losing 21-hydroxylase deficiency that was found to be homozygous for 2 "mild"pathogenic variants: V281L and S301Y. Both in silico and heterologous expression functional analysis demonstrated that co-occurrence of these 2 mutations in cis severely impairs the function of the 21-hydroxylase enzyme. Conclusions: This case has important implications for genetic counseling. Regarding this combination of 2 "mild"variants as having mild phenotypic effects could lead to inappropriate counseling of heterozygote carriers.

Año de publicación:

2021

Keywords:

  • salt-wasting
  • Genetics
  • Congenital adrenal hyperplasia
  • 21-hydroxylase

Fuente:

scopusscopus

Tipo de documento:

Article

Estado:

Acceso abierto

Áreas de conocimiento:

  • Genética
  • Genética

Áreas temáticas:

  • Fisiología humana
  • Ginecología, obstetricia, pediatría, geriatría
  • Enfermedades