Naslov
Screening for Mutations and Polymorphisms in Phosphomannomutase 2 Gene (PMM2) in Croatian Population

Autori
Šupraha Goreta, Sandra ; Dabelić, Sanja ; Štimac, Hrvoje ; Dumić, Jerka

Izvornik
Journal of research in pharmaceutical sciences (2303-6869) 1 (2014), 1; 19-27

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
CDG ; PMM2 gene ; SSCP analysis ; Croatian population

Sažetak
Introduction: Congenital disorders of glycosylation (CDGs) are a growing group of rare genetic disorders caused by defective glycosylation of glycoconjugates. The most common type of CDGs is PMM2-CDG, caused by reduced N- glycosylation due to phosphomannomutase 2 deficiency as a consequence of various mutations in PMM2 gene. The variations in the frequencies of healthy carriers for those mutations were observed among the populations of different geographic or ethnic origin. So far, no CDG-patient has been detected in Croatia. We screened healthy Croatian population for the presence of most common PMM2- CDG-related mutations p.Arg141His and p.Phe119Leu, as well as intragenic polymorphisms c.447+19T>C, c.447+22T>A, and c.348-56_348-55insATG in PMM2 gene. Materials and methods: Genomic DNA was isolated from blood samples obtained from 800 healthy unrelated Croatian residents. The exon 5 and parts of adjacent intronic sequences of PMM2 gene were amplified by PCR. For screening target mutations, single-strand conformation polymorphism (SSCP) analysis was used. All samples showing aberrant SSCP patterns (71) adequate number of randomly chosen ones with normal pattern (50) and positive control samples were additionally sequenced. Results: Mutations p.Arg141His and p.Phe119Leu have not been detected in analyzed population. The allele c.447+22A has been found among healthy individuals (frequency 0.25). The allele and genotype frequencies of analyzed polymorphisms are different comparing to other European populations. Conclusion: The absence of both mutations (p.Arg141His and p.Phe119Leu) and the estimated allele/genotype frequencies of intragenic polymorphisms in analyzed series suggest specificity of the Croatian population regarding these mutations/polymorphisms compared to other European populations.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

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