Molecular genetics and impact of residual in vitro phenylalanine hydroxylase activity on tetrahydrobiopterin responsiveness in Turkish PKU population.
Yazarlar (1)
Prof. Dr. Işıl ÖZER Kafkas Üniversitesi, Türkiye
| Makale Türü | Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale) | ||
| Dergi Adı | Molecular Genetics and Metabolism (Q2) | ||
| Dergi ISSN | 1096-7192 Dergi Bilgileri (2011) | ||
| Dergi Tarandığı Indeksler | SSCI | ||
| Makale Dili | Türkçe | Basım Tarihi | 02-2011 |
| Cilt / Sayı / Sayfa | 102 / 2 / 116–121 | DOI | 10.1016/j.ymgme.2010.11.158 |
| UAK Araştırma Alanları |
Çocuk Metabolizma Hastalıkları (Çocuk Sağlığı ve Hastalıkları)
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| Özet |
| Background: The prevalence of phenylalanine hydroxylase (PAH)-deficient phenylketonuria (PKU) in Turkey is high (1 in 6500 births), but data concerning the genotype distribution and impact of the genotype on tetrahydrobiopterin (BH4) therapy are scarce. Objective: To characterize the phenotypic and genotypic variability in the Turkish PKU population and to correlate it with physiological response to BH4 challenge. Methods: We genotyped 588 hyperphenylalaninemic patients and performed a BH4 loading test (20 mg/kg body weight) in 462 patients. Residual PAH activity of mutant proteins was calculated from available in vitro expression data. Data were tabulated in the BIOPKU database (www. biopku. org).Results: Eighty-eight mutations were observed, the most common missense mutations being the splice variant c. 1066-11G> A (24.6%). Twenty novel mutations were detected (11 missense, 4 splice site, and 5 deletion/insertions). Two mutations were observed in 540/588 patients (91.8%) but in 9 patients atypical genotypes with> 2 mutations were found 8 with p. R155H in cis with another variant) and in 19 patients mutations were found in BH4-metabolizing genes. The most common genotype was c. 1066-11G> A/c. 1066-11G> A (15.5%). Approximately 22% of patients responded to BH4 challenge. A substantial in vitro residual activity (average> 25% of the wild type enzyme) was associated with response to BH4. In homozygous genotypes (n= 206), both severity of the phenotype (r= 0.83) and residual PAH activity (r= 0.85) correlate with BH4 responsiveness. Conclusion: Together with the BH4 challenge, these data enable the genotype … |
| Anahtar Kelimeler |
| BH4 | Hyperphenylalaninemia | PAH | Phenylketonuria | PKU | Sapropterin |
Science Direct
Molecular genetics and impact of residual in vitro phenylalanine hydroxylase activity on tetrahydrobiopterin responsiveness in Turkish PKU population.
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Scopus | 84 |
| Google Scholar | 125 |