Massive parallel sequencing as a new diagnostic approach for phenylketonuria and tetrahydrobiopterin-deficiency in Thailand

BMC Medical Genetics

Research Article

Pongsathorn Chaiyasap¹  Chupong Ittiwut²  Chalurmpon Srichomthong²  Vorasuk Shotelersuk²  Kanya Suphapeetiporn³  Apiruk Sangsin⁴ 

[1] Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, 10330, Bangkok, Thailand;Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, 10330, Bangkok, Thailand;Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, 10330, Bangkok, Thailand;Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, 10330, Bangkok, Thailand;Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, 10330, Bangkok, Thailand;Division of Medical Genetics and Metabolism, Department of Pediatrics, Sor Kor Building 11th floor, King Chulalongkorn Memorial Hospital, 10330, Bangkok, Thailand;Department of Orthopedics, Faculty of Medicine, Chiang Mai University, 50200, Chiang Mai, Thailand;

关键词: Next generation sequencing;    Exome;    Hyperphenylalaninemia;    Phenylketonuria;    Tetrahydrobiopterin deficiency;    Newborn screening;   

DOI  :  10.1186/s12881-017-0464-x

 received in 2017-05-14, accepted in 2017-09-08,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundHyperphenylalaninemia (HPA) can be classified into phenylketonuria (PKU) which is caused by mutations in the phenylalanine hydroxylase (PAH) gene, and BH4 deficiency caused by alterations in genes involved in tetrahydrobiopterin (BH4) biosynthesis pathway. Dietary restriction of phenylalanine is considered to be the main treatment of PKU to prevent irreversible intellectual disability. However, the same dietary intervention in BH4 deficiency patients is not as effective, as BH4 is also a cofactor in many neurotransmitter syntheses.MethodWe utilized next generation sequencing (NGS) technique to investigate four unrelated Thai patients with hyperphenylalaninemia.ResultWe successfully identified all eight mutant alleles in PKU or BH4-deficiency associated genes including three novel mutations, one in PAH and two in PTS, thus giving a definite diagnosis to these patients. Appropriate management can then be provided.ConclusionThis study identified three novel mutations in either the PAH or PTS gene and supported the use of NGS as an alternative molecular genetic approach for definite diagnosis of hyperphenylalaninemia, thus leading to proper management of these patients in Thailand.

【 授权许可】

CC BY   
© The Author(s). 2017