title: Congenital disorder of glycosylation type Ia: searching for the origin of common mutations in PMM2.
abstract: Congenital Disorders of Glycosylation (CDG) are a group of recessive genetic disorders characterized by hypoglycosylation of glycoproteins. CDG-Ia, the most common type, is caused by mutations in the PMM2 gene, coding for a phosphomannomutase (PMM2; EC 5.4.2.8). The mutational spectrum of PMM2 comprises more than 80 different mutations but one of them, R141H, is particularly interesting due to its high frequency among CDG-Ia patients worldwide. In contrast, other mutations are ethnically or geographically restricted, such as D65Y which is only found in patients of Iberian ancestry. In the present study a population genetic approach was used in an attempt to clarify the origins of two important disease causing mutations: R141H and D65Y. Based on SNP and STR genotypic analysis, we ascertained an association between the R141H substitution and a particular haplotype, suggesting a common origin for all the mutated chromosomes. Similar results were found for D65Y, although the associated haplotype was different from that of R141H, suggesting independent origins for these two mutations. Our results enable us to infer an Iberian origin for the D65Y mutation.
authors.affiliation: IGMJM - Institute of Medical Genetics Jacinto de Magalhães, Porto, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Quelhas
authors.forename: R
authors.initials: R
authors.lastname: Quental
authors.forename: L
authors.initials: L
authors.lastname: Vilarinho
authors.forename: A
authors.initials: A
authors.lastname: Amorim
authors.forename: L
authors.initials: L
authors.lastname: Azevedo
mesh_terms: D002239:Carbohydrate Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D002675:Child, Preschool; D019143:Evolution, Molecular; D005260:Female; D006031:Glycosylation; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010641:Phenotype; D017875:Phosphotransferases (Phosphomutases) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D011247:Pregnancy
chemical_list: D017875:Phosphotransferases (Phosphomutases); C519582:phosphomannomutase 2, human