CDG-Id caused by homozygosity for an ALG3 mutation due to segmental maternal isodisomy UPD3(q21.3-qter)

Eur J Med Genet. Apr-Jun 2005;48(2):153-8. doi: 10.1016/j.ejmg.2005.01.002. Epub 2005 Feb 17.

Abstract

We report on a patient with a congenital disorder of glycosylation type Id (CDG-Id) caused by a homozygous mutation in the ALG3 gene, which results from a de novo mutation in combination with a segmental maternal uniparental isodisomy (UPD). The patient presented with severe psychomotor delay, primary microcephaly, and opticus atrophy, compatible with a severe form of CDG. Isoelectric focusing of transferrin showed a type I pattern and lipid-linked oligosaccharide analysis showed an accumulation of dol-PP-GlcNAc2Man5 in patient's fibroblasts suggesting a defect in the ALG3 gene. A homozygous ALG3 missense mutation p.R266C (c.796C > T) was identified. Further evaluation revealed that neither the mother nor the father were carrier of the p.R266C mutation. Marker analysis revealed a segmental maternal isodisomy for the chromosomal region 3q21.3-3qter. UPD for this region has not been described before. More important, the combination of UPD with a de novo mutation is an exceptional coincidence and an extraordinary observation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Metabolism, Inborn Errors / enzymology*
  • Carbohydrate Metabolism, Inborn Errors / genetics*
  • Child, Preschool
  • Chromosome Mapping
  • Chromosomes, Human, Pair 3 / genetics*
  • DNA Mutational Analysis
  • Female
  • Glycosylation
  • Homozygote
  • Humans
  • In Situ Hybridization, Fluorescence
  • Mannosyltransferases / genetics*
  • Microcephaly / genetics
  • Mutation, Missense*
  • Optic Atrophies, Hereditary / genetics
  • Phenotype
  • Psychomotor Disorders / genetics
  • Syndrome
  • Uniparental Disomy*

Substances

  • ALG3 protein, human
  • Mannosyltransferases