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Spectrum of PAH gene variants in Jordanian patients with phenylalanine hydroxylase deficiency

  • Authors:
    • Rajaa Fathallah
    • Khadeeja Al‑Rashed
    • Alaa Arafat
    • Hanan Awwad
    • Latifa Maraqa
    • Mohammed El‑Khateeb
    • Mohammad Shboul
  • View Affiliations / Copyright

    Affiliations: National Center for Diabetes, Endocrinology and Genetics, Amman 11942, Jordan, PKU and Genetic Consultation Clinic, Ministry of Health, Amman 86, Jordan, Department of Medical Laboratory Sciences, Faculty of Medical Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan
    Copyright: © Fathallah et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 151
    |
    Published online on: July 3, 2025
       https://doi.org/10.3892/br.2025.2029
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Abstract

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by pathogenic variants in the phenylalanine hydroxylase (PAH) gene. PKU is considered as one of the most common autosomal recessive diseases in Jordan; however, the spectrum of gene variants is yet to be determined. The present study aimed to identify the PAH genetic variants in a cohort of Jordanian children diagnosed with PKU. A total of 77 affected patients from 50 families were enrolled in the present study. All exons as well as exon‑intron boundaries of the PAH gene were analyzed by Sanger sequencing. Segregation analysis was performed on the available family members. A total of 23 distinct PAH variants were identified with a detection rate of 100%. All variants were either pathogenic or likely pathogenic. These variants included 9 missense (39.1%), 6 splice site (26.1%), 4 frameshift (17.4%), 2 nonsense (8.7%) and 2 in‑frame deletion (8.7%) variants. Among these variants, one was novel [c.781del; p.(Arg261Glufs80)]. The present study highlighted the wide spectrum of disease‑causing variants in the PAH gene among Jordanian patients. The findings also underscore the importance of establishing region‑specific genetic screening. Early genetic diagnosis of PKU will facilitate timely treatment and management of affected patients, risk stratification and genetic counseling, thereby reducing the burden of PKU in Jordan.
View Figures

Figure 1

The categories of the identified
variants and their distribution in PAH domains and the PAH
gene. (A) Type of variants identified and their frequency. (B) The
distribution of PAH variants in PAH domains. (C) The
distribution of detected variants in the PAH gene. PAH,
phenylalanine hydroxylase.

Figure 2

Electropherogram of the novel variant
[c.781del; p.(Arg261Glufs80)]. The parents are heterozygous and the
affected children are homozygous.
View References

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Copy and paste a formatted citation
Spandidos Publications style
Fathallah R, Al‑Rashed K, Arafat A, Awwad H, Maraqa L, El‑Khateeb M and Shboul M: Spectrum of <em>PAH</em> gene variants in Jordanian patients with phenylalanine hydroxylase deficiency. Biomed Rep 23: 151, 2025.
APA
Fathallah, R., Al‑Rashed, K., Arafat, A., Awwad, H., Maraqa, L., El‑Khateeb, M., & Shboul, M. (2025). Spectrum of <em>PAH</em> gene variants in Jordanian patients with phenylalanine hydroxylase deficiency. Biomedical Reports, 23, 151. https://doi.org/10.3892/br.2025.2029
MLA
Fathallah, R., Al‑Rashed, K., Arafat, A., Awwad, H., Maraqa, L., El‑Khateeb, M., Shboul, M."Spectrum of <em>PAH</em> gene variants in Jordanian patients with phenylalanine hydroxylase deficiency". Biomedical Reports 23.3 (2025): 151.
Chicago
Fathallah, R., Al‑Rashed, K., Arafat, A., Awwad, H., Maraqa, L., El‑Khateeb, M., Shboul, M."Spectrum of <em>PAH</em> gene variants in Jordanian patients with phenylalanine hydroxylase deficiency". Biomedical Reports 23, no. 3 (2025): 151. https://doi.org/10.3892/br.2025.2029
Copy and paste a formatted citation
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Spandidos Publications style
Fathallah R, Al‑Rashed K, Arafat A, Awwad H, Maraqa L, El‑Khateeb M and Shboul M: Spectrum of <em>PAH</em> gene variants in Jordanian patients with phenylalanine hydroxylase deficiency. Biomed Rep 23: 151, 2025.
APA
Fathallah, R., Al‑Rashed, K., Arafat, A., Awwad, H., Maraqa, L., El‑Khateeb, M., & Shboul, M. (2025). Spectrum of <em>PAH</em> gene variants in Jordanian patients with phenylalanine hydroxylase deficiency. Biomedical Reports, 23, 151. https://doi.org/10.3892/br.2025.2029
MLA
Fathallah, R., Al‑Rashed, K., Arafat, A., Awwad, H., Maraqa, L., El‑Khateeb, M., Shboul, M."Spectrum of <em>PAH</em> gene variants in Jordanian patients with phenylalanine hydroxylase deficiency". Biomedical Reports 23.3 (2025): 151.
Chicago
Fathallah, R., Al‑Rashed, K., Arafat, A., Awwad, H., Maraqa, L., El‑Khateeb, M., Shboul, M."Spectrum of <em>PAH</em> gene variants in Jordanian patients with phenylalanine hydroxylase deficiency". Biomedical Reports 23, no. 3 (2025): 151. https://doi.org/10.3892/br.2025.2029
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