Genetic analysis of eighteen patients from Gansu province with Tetrahydrobiopterin deficiency
10.3760/cma.j.cn511374-20221028-00727
- VernacularTitle:甘肃地区四氢生物蝶呤缺乏症18例患者的遗传学分析
- Author:
Chuan ZHANG
1
;
Xinyuan TIAN
;
Yupei WANG
;
Panpan MA
;
Xue CHEN
;
Bingbo ZHOU
;
Qinghua ZHANG
;
Shengju HAO
;
Ling HUI
;
Zhe YIN
;
Zongfu CAO
Author Information
1. 甘肃省妇幼保健院(甘肃省中心医院)，甘肃省出生缺陷与罕见病临床医学研究中心/医学遗传中心，兰州 730050
- Keywords:
Tetrahydrobiopterin deficiency;
Genetic analysis;
Intervention treatment;
Genetic counseling;
Pedigree
- From:
Chinese Journal of Medical Genetics
2024;41(2):129-133
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic basis of eighteen patients with tetrahydrobiopterin deficiency (BH4D) from Gansu Province.Methods:Eighteen 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.Results:All 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). Conclusion:Genetic 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.
