Genetic analysis of eighteen patients from Gansu province with Tetrahydrobiopterin deficiency
Zhang Chuan, Tian Xinyuan, Wang Yupei, Ma Panpan, Chen Xue, Zhou Bingbo, Zhang Qinghua, Hao Shengju, Hui Ling, Yin Zhe, Cao Zongfu
Abstract
ObjectiveTo explore the genetic basis of eighteen patients with tetrahydrobiopterin deficiency (BH4D) from Gansu Province.
MethodsEighteen patients diagnosed with BH4D at Gansu Provincial Maternal and Child Health Care Hospital from January 2018 to December 2021 were selected as the study subjects. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing.
ResultsAll of the thirty-six alleles of the eighteen patients were successfully determined by molecular genetic testing. Sixteen patients were found to harbor variants of the PTS gene, and two had harbored variants of the QDPR gene. Ten variants were detected in the PTS gene, with the most common ones being c. 259C>T (34.38%) and c. 286G>A (15.63%). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 259C>T was classified as a pathogenic variant, whilst the c. 286G>A, c. 166G>A, c. 200C>T, c. 272A>G, c. 402A>C, c. 421G>T, c. 84-291A>G and c. 317C>T were classified as likely pathogenic variants. A novel c. 289_290insCTT variant was classified as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PP3+ PP4). The two variants (c.478C>T and c. 665C>T) detected in the QDPR gene were both classified as variants of uncertain significance (PM1+ PM2_Supporting+ PP3+ PP4).
ConclusionGenetic testing has clarified the pathogenic variants in these BH4D patients, which has enabled timely and accurate clinical intervention and treatment, and provided a reference for genetic counseling and reproductive guidance for their families.
Key words:
Tetrahydrobiopterin deficiency; Genetic analysis; Intervention treatment; Genetic counseling; Pedigree
Contributor Information
Zhang Chuan
Center for Medical Genetics, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Gansu Provincial Maternity and Child Health Care Hospital, Lanzhou, Gansu 730050, China
Tian Xinyuan
Center for Medical Genetics, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Gansu Provincial Maternity and Child Health Care Hospital, Lanzhou, Gansu 730050, China
Wang Yupei
Center for Medical Genetics, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Gansu Provincial Maternity and Child Health Care Hospital, Lanzhou, Gansu 730050, China
Ma Panpan
Center for Medical Genetics, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Gansu Provincial Maternity and Child Health Care Hospital, Lanzhou, Gansu 730050, China
Chen Xue
Center for Medical Genetics, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Gansu Provincial Maternity and Child Health Care Hospital, Lanzhou, Gansu 730050, China
Zhou Bingbo
Center for Medical Genetics, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Gansu Provincial Maternity and Child Health Care Hospital, Lanzhou, Gansu 730050, China
Zhang Qinghua
Center for Medical Genetics, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Gansu Provincial Maternity and Child Health Care Hospital, Lanzhou, Gansu 730050, China
Hao Shengju
Center for Medical Genetics, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Gansu Provincial Maternity and Child Health Care Hospital, Lanzhou, Gansu 730050, China
Hui Ling
Center for Medical Genetics, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Gansu Provincial Maternity and Child Health Care Hospital, Lanzhou, Gansu 730050, China
Yin Zhe
National Research Institute for Family Planning, National Human Genetic Resources Center, Beijing 100081, China
Cao Zongfu
National Research Institute for Family Planning, National Human Genetic Resources Center, Beijing 100081, China
