Complex Mutation Analysis of the PAH Gene in Slovak Patients Affected by Phenylketonuria

Česká verzia

Authors: E. Polák ¹; A. Ficek ¹; M. Baldovič ^1,2; E. Feráková ¹; A. Šoltýsová ¹; J. Strnová ³; O. Ürge ³; L. Kovács ⁴; Ľ. Kádaši ^1,2
Authors place of work: Katedra molekulárnej biológie PrírF UK, Bratislava vedúci doc. RNDr. Ľ. Kádasi, DrSc. ¹; Ústav molekulárnej fyziológie a genetiky SAV, Bratislava vedúci doc. RNDr. Ľ. Kádasi, DrSc. ²; Klinika deti a dorastu Andreja Getlíka. SZU, Bratislava prednostka doc. MUDr. K. Furková, CSc., mim. prof. ³; 2. detská klinika LFUK a DFNsP, Bratislava prednosta prof. MUDr. L. Kovács, DrSc, MPH ⁴
Published in the journal: Čes-slov Pediat 2008; 63 (10): 528-534.
Category: Original Papers

Summary

This work continues previous studies to detect molecular basis of phenylketonuria in Slovak patients. DHPLC screening for all 13 exons of the PAH gene was introduced and optimized. DNA samples from 48 subjects with biochemically proven phenylketonuria were analyzed in whom direct DNA diagnostics (detection of 11 most frequent mutations) allowed to identify mutations on only one or none PKU chromosome. In this study, 16 new mutations were detected, (Q20X, F39L, R68S, F233I, R176X, P281L, R270I, T278N, R243X, A300S, I306V, W326X, L348V, S349P, E390G, Y387X), which were not known in this population as yet. Individual mutations were allocated to the appropriate phenotypic categories of phenylketonuria.

The present results will be applied for routine diagnostic practice of PKU in this country. In addition to causative mutations, several genetic polymorphisms were detected in introns, but also in the exons of the PAH gene. Up to date, 84,3% of Slovak PKU alleles are already identified, detection of the remaining 15,7 % needs additional studies and investigational approaches.

Key words:
phenylketonuria, mutations, mutational analysis, DNA diagnostics

Zdroje

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