Naslov
Detection of mutations in arylsulfatase A gene in cerebral palsy - two different approaches

Autori
Mlinac, Kristina ; Kalanj Bognar, Svjetlana ; Furač, Ivana ; Grubešić, Zdravko

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

Izvornik
Abstract book of the 3rd ESF Functional Genomics Conference / - Innsbruck, 2008, 107-108

Skup
3rd ESF Functional Genomics Conference: Functional Genomics and Disease

Mjesto i datum
Innsbruck, Austrija, 01.10.2008. - 04.10.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
arylsulfatase A; cerebral palsy

Sažetak
Lower activity of lysosomal enzyme arylsulfatase A (ASA, EC 3.1.6.8) was observed in leukocytes of patients with cerebral palsy, a neurodevelopmental disorder of complex ethiopathogenesis. The aim of this study was to estimate possible contribution of four described mutations in ASA gene: two most common mutations associated with ASA-pseudodeficiency (N350S and 1524+95 A-G) and two most common mutations underlying metachromatic leukodystrophy, MLD (P426L and 459+1 G-A). Mutations associated with metachromatic leukodystrophy were detected using two different methods previously described, but unexpectedly different results were obtained. According to the first method, P426L and 459+1 G-A mutations were detected by digestion with Xba I and Pst I, respectively. Using this method, the 459+1 G-A mutation was detected in 9 of 56 individuals, while P426L mutation was found to be present in even 12 of 64 individuals. Estimated frequencies of determined mutations were thus surprisingly high in the analyzed group of patients (8 % and 9.37 %, respectively). In order to check the results, we used another genotyping method, which detects the polymorphisms with different restriction enzymes, Aci I (for the P426L mutation) and Bst NI (for the 459+1 G-A mutation). In analyzed group of patients no mutation was found and thus no confirmation of previous results was obtained. In order to clarify which of the methods would give more reliable results, we sequenced fragments of ASA gene amplified with two different pair of primers, according to two different methods described for estimation of MLD mutations. Samples with and without mutation were sequenced and obtained results were compared for two different genotyping approaches. In conclusion, ASA activity found to be lower in patients with cerebral palsy may be related to detected mutations associated with ASA pseudodeficiency and MLD, and most probably with yet undescribed mutated sites in the ASA gene.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA