Naslov
The study on the frequency of heterozygotes for Y131H mutation in ALG6 gene in Croatian population revealed 5 novel mutations

Autori
Supraha Goreta, Sandra ; Dabelic, Sanja ; Dumic, Jerka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts / Strelec, Ivica ; Glavaš-Obrovac ; Ljubica - Zagreb : Hrvatsko Društvo za Biotehnologiju, 2008, 49-49

ISBN
978-953-95551-2-0

Skup
Congress of the Croatian Society of Biochemistry and Molecular Biology

Mjesto i datum
Osijek, Hrvatska, 17.09.2008. - 20.09.2008

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
CDG-Ic; ALG6 gene; mutations

Sažetak
Congenital disorders of glycosylation (CDGs) are a growing group of autosomal recessive diseases caused by deficient assembly or processing of glycoproteins. The primary defects either impair the formation of the lipid-linked oligosaccharide precursor of N-linked glycosylation (CDGs type I) or affect processing of the protein-bound sugar chains (CDGs type II). Although only  1000 CDG patients were diagnosed so far, the true incidence was estimated to be much higher (based on frequency analysis for certain common mutations). The clinical spectrum of the different types of CDGs discovered so far is highly variable, ranging from disorders restricted to specific organs to severe multisystemic disorders. Because of the resemblance of CDG symptoms to some other diseases, especially neurological ones, CDGs are often under- or misdiagnosed. The second most frequent type of CDGs, CDG-Ic is caused by mutations in ALG6 gene that encode Man9GlcNAc2-PP-Dol  1, 3-glucosyltransferase. The frequencies of heterozygotes for specific mutations, as well as CDG patients were shown to be specific for every population. Until now no patient with CDG syndrome was detected in Croatia. Here we present the results of the study on the frequency of Y131H mutation in the population of Croatia. The blood samples of 600 healthy volunteers were collected on Blood Stain Cards&reg ; and the presence of the target mutation (391T>C in exon 5) was examined by real-time PCR (TaqMan SNP Genotyping Assay). Surprisingly, eight homozygotes for Y131H were detected, but since the samples were obtained from healthy persons, direct sequencing was employed for checking these weird results. It revealed 3 novel polymorphisms in exon 5 of ALG6 gene (383T C, 390G>A and 429G C) and in 2 novel polymorphisms (IVS5+17C>T and IVS5+34G>A) in downstream intervening sequence. It seems that presence of these until now unknown mutation caused incorrect/inappropriate binding of the designed probes and sondes thus yielding false positive results. The base substitution T C on the position 383 does not cause amino acid substitution, but 390G>A and 429G C cause substitution of V128A and K143N, respectively. Finally, the frequency of heterozygotes for Y131H was found to be 6.53% that is 3 times higher than in the United States. If the obtained results are valid for Croatian population (1/15) the estimated incidence of homozygotes should be 1 in 1000, suggesting  4500 CDG-Ic patients should be in Croatia.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA