Articles Vol. 64 No. 2 15/03/2023

9. NEXT GENERATION SEQUENCING REVEALED THE GENETIC LANDSCAPE OF DISEASE-ASSOCIATED VARIANTS OF PHENYLKETONURIA

Phan Ngoc Phu Quy1,2, Tang Hung Sang3,4, Giang Hoa3,4, Doan Thi Kim Phuong5,6, Hoang Thu Lan5,6, Hoang Thi Ngoc Lan5,6, Luong Thi Lan Anh5,6
1 Forensic Medicine Center Ho Chi Minh City
2 Trung tâm Pháp y thành phố Hồ Chí Minh
3 Gene Solutions
4 Viện Di truyền Y học
5 Hanoi Medical University
6 Trường Đại học Y Hà Nội
Corresponding author: quyphan2461993@gmail.com
DOI: 10.52163/yhc.v64i2.611
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Keywords
Phenylketonuria (PKU), variant, carriers screening, Next Generation Sequencing.
Abstract

Phenylketonuria (PKU) is an autosomal recessive disorder caused by the PAH gene located on
chromosome 12. The disease is characterized by a defect in the enzyme phenylalanine hydroxylase
(PAH), causing elevated levels of phenylalanine (Phe) in the blood and subsequently leading to
neurotoxicity and mental disability. The world prevalence of PKU was about 1 in 10,000 - 20,000
newborns, still, data about PKU carriers and the disease-associated variant spectra in Vietnamese
people is minimal. The advent of Next Generation Sequencing (NGS) allows the simultaneous
detection of multiple genetic variants, including novel variants in numerous patients within a single
test, substantially reducing the testing cost. Objectives: Our study aimed to screen the carrier
frequency of the PAH gene and uncover variant spectra of this disease in Vietnamese women.
Methods: 2937 women who came for a prenatal routine healthcare check at the Center of Clinical
Genetics and Genomics - Ha Noi Medical University Hospital and Gene Solutions were screened
for disease-associated variants of the PAH gene employing NGS. Results: Of 2937 participants,
70 women were carriers (2.4%), and 12 different disease-associated variants were detected: R408Q
(1/2937), V388M (2/2937), P314T (2/2937), E280K (1/2937), R241fs (1/2937), R241C (1/2937),
Y206* (1/2937), Y204C (1/2937), Q172H (56/2937), H170Q (2/2937), R111* (1/2937), L41F
(1/2937). Q172H was predominant in our study. There are two rare variants that allele frequency
has not been reported in ClinVar and Ensemble: L41F và R241fs. Conclusion: The data from our
research will inform policymakers in constructing cost-effective genetic metabolic carrier screening
programs.

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