engleski

Screening for mutations in phosphomannomutase 2 (PMM2) gene

Congenital disorder of glycosylation (CDG) Ia (MIM≠ 212065) is an autosomal recessive multi-organ disease characterized by severe dysfunction of central and peripheral nervous system. It is caused by a defective N-linked glycosylation due to phosphomannomutase (PMM) deficiency as a consequence of mutations in PMM2 gene. More than 85 different mutations in the PMM2 gene known so far are widespread over the gene consisting of 8 exons. The most frequent ones are R141H and F119L, both caused by a single base mutation in exon 5 of PMM2 gene, 422G>A and 357C>A, respectively. We have recently undertaken a comprehensive project with a purpose to determine the frequency of these and some other mutations and polymorphisms in genes related to CDGs in Croatian population. Until now no patient with CDG was detected in Croatian population. Here we present the results of screening for mutations in the exon 5 and parts of intervening sequences IVS4 and IVS5 of PMM2 gene in Croatian population. The study encompassed 104 unrelated individuals. Screening was performed by PCR-SSCP analysis (6% polyacrilamide electrophoresis, 15  C). 10 fragments that showed aberrant patterns were additionally sequenced on ABI Prism 310 Genetic Analyzer. R141H and F119L mutations were not found in the analyzed group. However, we detected four homozygotes (IVS5+19T/T) and six heterozygotes (IVS5+19T/C) for intragenic single nucleotide polymorphism (SNP) IVS5+19T/C, while all 10 individuals were homozygous for SNP IVS5+22T/T. One of the heterozygotes for IVS5+19T/C was also a heterozygote for deletion of 3bp (ATG) on the position -58 in intron 4 (IVS4-58delATG).

CDG I ; phosphomannomutase 2 ; PMM2 gene ; mutations

nije evidentirano