NUK - logo
VSE knjižnice (vzajemna bibliografsko-kataložna baza podatkov COBIB.SI)
  • Five novel mutations and two large deletions in a population analysis of the phenylalanine hydroxylase gene
    Grošelj, Urh ...
    Mutational spectrum of the phenylalanine hydroxylase (PAH) deficiency was investigated in 107 families (90% of the Slovene PKU population). The entire coding region of the PAH gene was analyzed with ... dHPLC to select the samples where subsequently the automated sequencing analysis was performed. MLPA analysis was performed to identify large deletions, which were later confirmedwith long-range PCR. Correlations with patients' phenotypes and genotype-based predictions of BH(4)-responsiveness were assessed. Altogether, disease-causing mutations were identified on 209 alleles (detection rate 97.7%). A spectrum of 36 different disease-causing mutations was identified: 20 missense mutations (80% of the alleles), eight splicing mutations (13% of the alleles), one nonsense mutation (0.5% of the alleles), four small deletions with frame shift (6% of the alleles), one small insertion with frameshift (0.5% of the alleles), and two large deletions (2% of the alleles).The most frequent mutation was p.R408W in exon 12, representing 29% of the alleles, which is in concordance with other neighboring and/or Slavic PKU populations. Other common mutations were: p.R158Q, p.A403V, p.P281L and p.E390G, accounting for 9%, 7%, 7% and 7% of the alleles respectively. Five novel mutations were detected: c.43_44insAG, c.56_59+1delACAGG, p.V45A, p.L62Pand p.R157S. Large deletion of exon 5 (EX5del955) was found in three patients and a deletion of exon 3 (EX3del4765) in one patient. A spectrum of 64 different genotypes was found, seven of them accounting for over than a third of all families. Among thirteen families with homozygous mutation (13% of the PKU population), 10 had p.R408W, two had p.R158Q and one had p.E390G. Among 107 families, 58 were classified as classic PKU (54.2%), 28 as mild PKU (25.9%) and 21 as MHP (19.6%). Twenty-six different genotypes (40.6%) were predicted to be BH(4)-responsive, represented by 38 different families (35.5%).
    Vir: Molecular genetics and metabolism. - ISSN 1096-7192 (Vol. 106, no. 2, 2012, str. 142-148)
    Vrsta gradiva - članek, sestavni del ; neleposlovje za odrasle
    Leto - 2012
    Jezik - angleški
    COBISS.SI-ID - 29876441
    DOI

Vnos na polico