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Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome)

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Matthijs, Gert Schollen, Els Pardon, Els Veiga-da-Cunha, Maria [UCL] Jaeken, Jaak Van Schaftingen, Emile [UCL]

Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1 or Jaeken syndrome) is the prototype of a class of genetic multisystem disorders characterized by defective glycosylation of glycoconjugates(1-4). It is mostly a severe disorder which presents neonatally. There is a severe encephalopathy with axial hypotonia, abnormal eye movements and pronounced psychomotor retardation, as well as a peripheral neuropathy, cerebellar hypoplasia and retinitis pigmentosa. The patients show a peculiar distribution of subcutaneous fat, nipple retraction and hypogonadism. There is a 20% lethality in the first years of life due to severe infections, liver insufficiency or cardiomyopathy(2,3,5). CDG1 shows an autosomal recessive mode of inheritance and has been mapped to chromosome 16p(6,7). Most patients show a deficiency of phosphomannomutase (PMM)(8), an enzyme necessary for the synthesis of GDP-mannose. We have cloned the PMM1 gene, which is on chromosome 22q13 (ref, 9), We now report the identification of a second human PMM gene, PMM2, which is located on 16p13 and which encodes a protein with 66% identity to PMM1. We found eleven different missense mutations in PMM2 in 16 CDG1 patients from different geographical origins and with a documented phosphomannomutase deficiency. Our results give conclusive support to the biochemical finding that the phosphomannomutase deficiency is the basis for CDG1.

Document type Article de périodique (Journal article) – Article de recherche
Publication date 1997
Language Anglais
Journal information "Nature Genetics" - Vol. 16, no. 1, p. 88-92 (1997)
Peer reviewed yes
Publisher Nature Publishing Group (New York)
issn 1061-4036
e-issn 1546-1718
Publication status Publié
Affiliation UCL - MD/BICL - Département de biochimie et de biologie cellulaire
MESH Subject Tissue Distribution ; Sequence Homology, Amino Acid ; Sequence Analysis, DNA ; Saccharomyces cerevisiae Proteins ; Polymorphism, Genetic ; Polymerase Chain Reaction ; Phosphotransferases (Phosphomutases) - genetics ; Pancreas - enzymology ; Mutation ; Molecular Sequence Data ; Liver - enzymology ; Humans ; Heterozygote ; Fungal Proteins - genetics ; Congenital Disorders of Glycosylation - genetics ; Cloning, Molecular ; Chromosomes, Human, Pair 16 ; Chromosome Mapping ; Blotting, Southern ; Blotting, Northern ; Base Sequence ; Amino Acid Sequence
Links
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Bibliographic reference Matthijs, Gert ; Schollen, Els ; Pardon, Els ; Veiga-da-Cunha, Maria ; Jaeken, Jaak ; et. al. Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome). In: Nature Genetics, Vol. 16, no. 1, p. 88-92 (1997)
Permanent URL http://hdl.handle.net/2078.1/46301