| Yazarlar |
Doç. Dr. Işıl ÖZER
Kafkas Üniversitesi, Türkiye |
| 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 (20mg/kg bw) 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-based classification of BH4 responsiveness and document importance of residual PAH activity. This first report of a large-scale genotype assessment in a population of Turkish PKU patients also documents a high prevalence (47%) of the severe classic phenotype. © 2010 Elsevier Inc. |
| Anahtar Kelimeler |
| BH 4 | Hyperphenylalaninemia | PAH | Phenylketonuria | PKU | Sapropterin |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
| Dergi Adı | Molecular genetics and metabolism |
| Dergi ISSN | 1096-7192 |
| Dergi Tarandığı Indeksler | SSCI |
| Dergi Grubu | Q4 |
| Makale Dili | Türkçe |
| Basım Tarihi | 02-2011 |
| Cilt No | 102 |
| Sayı | 2 |
| Sayfalar | 116 / |
| Doi Numarası | 10.1016/j.ymgme.2010.11.158 |
| Atıf Sayıları | |
| SCOPUS | 79 |
| Google Scholar | 120 |
