title: CDG-Id caused by homozygosity for an ALG3 mutation due to segmental maternal isodisomy UPD3(q21.3-qter).
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.
authors.affiliation: Center for Human Genetics, UZ Leuven, Leuven, Belgium. Els.Schollen@uz.kuleuven.ac.be
authors.forename: E
authors.initials: E
authors.lastname: Schollen
authors.forename: S
authors.initials: S
authors.lastname: Grünewald
authors.forename: L
authors.initials: L
authors.lastname: Keldermans
authors.forename: B
authors.initials: B
authors.lastname: Albrecht
authors.forename: C
authors.initials: C
authors.lastname: Körner
authors.forename: G
authors.initials: G
authors.lastname: Matthijs
mesh_terms: D002239:Carbohydrate Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics*; D002675:Child, Preschool; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006031:Glycosylation; D006720:Homozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008364:Mannosyltransferases / Q000235:genetics*; D008831:Microcephaly / Q000235:genetics; D020125:Mutation, Missense; D015418:Optic Atrophies, Hereditary / Q000235:genetics; D010641:Phenotype; D011596:Psychomotor Disorders / Q000235:genetics; D013577:Syndrome; D024182:Uniparental Disomy
chemical_list: C489947:ALG3 protein, human; D008364:Mannosyltransferases