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Assessment of Pathogenic Variants in the PAH Gene and Genotype–Phenotype Correlation in Phenylketonuria Patients from Turkey

Biochemical Genetics · Şubat 2025

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YÖKSİS Kayıtları
Assessment of Pathogenic Variants in the PAH Gene and Genotype–Phenotype Correlation in Phenylketonuria Patients from Turkey
Biochemical Genetics · 2025 SCI-Expanded
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Makale Bilgileri

DergiBiochemical Genetics
Yayın TarihiŞubat 2025
Cilt / Sayfa63 · 896-905
Özet This study aims to determine the allele and genotype frequency, evaluate genotype–phenotype correlation and contribute to the spectrum of pathogenic variants in the PAH gene. Ninety-three individuals diagnosed with PKU were included in the study. Next-generation sequencing was utilized for detecting variants in the PAH gene. Copy Number Variations in patients without biallelic pathogenic variant were investigated by Multiplex Ligation-dependent Probe Amplification method. Genotype–phenotype correlations and genotype-based phenotype predictions were examined by comparing molecular test results with BIOPKUdb database. The clinical distributions of the patients were as follows: classic PKU 21% (n = 19), mild PKU 3% (n = 3), and mild hyperphenylalaninemia 76% (n = 71), respectively. Thirty-nine distinct variants and 70 distinct genotypes were found in patients. The most frequently observed variant was p.(Ala300Ser) (13.9%) and the most frequently observed genotype was p.[Ala300Ser];[Ala300Ser] (5.6%). Compound heterozygous genotypes (%69) were more prevalent than homozygous genotypes. A novel variant, c.441+4A>C, was observed. Predicted metabolic phenotypes in the database showed consistency with patient phenotypes (n = 33/41). BH4 responsiveness showed partial consistency with database predictions (n = 13/25). Establishing genotype–phenotype correlations can facilitate personalized management approaches. Overall, this study contributes to understanding the genetic basis and clinical course of PKU.

Yazarlar (8)

1
Özgür Balasar
ORCID: 0000-0002-2945-9355
2
Banu Kadıoğlu Yılmaz
3
Müşerref Başdemirci
ORCID: 0000-0001-9012-9307
4
Hatice Koçak Eker
ORCID: 0000-0003-2735-6739
5
Büşra Eser Çavdartepe
ORCID: 0000-0002-3023-302X
6
Levent Şimşek
ORCID: 0000-0001-7729-3970
7
Ebru Tunçez
ORCID: 0000-0002-0258-7779
8
Fahrettin Duymus

Anahtar Kelimeler

Genotype–phenotype correlation Novel variant PAH gene Phenylketonuria

Kurumlar

Konya City Hospital
Konya Turkey
Selçuk Tip Fakültesi
Konya Turkey

Metrikler

1
Atıf
8
Yazar
4
Anahtar Kelime