Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature

Mol Genet Metab. 2019 Dec;128(4):409-414. doi: 10.1016/j.ymgme.2019.08.007. Epub 2019 Aug 26.

Abstract

ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder caused by a deficiency of dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which presents with intellectual disability, hypotonia, dysmorphic features, low IgG levels with recurrent infections, male genital hypoplasia, and coagulation abnormalities. We report a unique family with three affected individuals, including two older brothers with only cognitive and coagulation defects and a younger brother who died from a severe multisystem disease at age 18 months. The two living brothers are the oldest and mildest cases of ALG12-CDG described thus far. Whole exome sequencing of the older brothers revealed a previously described c.1001delA (p.N334TfsX15) pathogenic variant and a c.671C > T (p.T224 M) variant of uncertain significance in ALG12. Our cases broaden the recognized genetic and phenotypic spectrum of this disorder and suggest a role for other genetic and environmental factors in modulating disease phenotype.

Keywords: ALG12; ALG12-CDG; CDG; Congenital disorder of glycosylation.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Congenital Disorders of Glycosylation / diagnosis*
  • Congenital Disorders of Glycosylation / genetics*
  • DNA Mutational Analysis
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Humans
  • Immunoglobulin G / blood
  • Male
  • Mannosyltransferases / genetics*
  • Mutation*
  • Phenotype*

Substances

  • Immunoglobulin G
  • Mannosyltransferases

Supplementary concepts

  • Congenital disorder of glycosylation type 1G