首页|甘肃地区四氢生物蝶呤缺乏症18例患者的遗传学分析

甘肃地区四氢生物蝶呤缺乏症18例患者的遗传学分析

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目的 探讨甘肃地区18例四氢生物蝶呤缺乏症(BH4D)患者的遗传学特征。 方法 选择2018年1月至2021年12月由甘肃省妇幼保健院医学遗传中心确诊的18例甘肃籍BH4D患者作为研究对象，对其进行全外显子组测序分析，并对候选变异进行Sanger测序家系验证。 结果 18例BH4D患者的36个等位基因均被成功检出，检出率为100.0%。其中16例是由PTS基因变异所致，2例是由QDPR基因变异所致。PTS基因共检测出10种不同的变异，其中热点变异为c.259C>T(34.38%)及c.286G>A(15.63%)。c.259C>T为已报道致病性变异，c.286G>A、c.166G>A、c.200C>T、c.272A>G、c.402A>C、c.421G>T、c.84-291A>G、c.317C>T为已报道的可能致病性变异。c.289_290insCTT既往未见报道，根据美国医学遗传学与基因组学学会变异相关指南评级为可能致病性变异(PM1＋PM2_Supporting＋PM3＋PP3＋PP4)。QDPR基因的c.478C>T和c.665C>T均被评级为临床意义未明变异(PM1＋PM2_Supporting＋PP3＋PP4)。 结论 基因检测明确了上述研究BH4D家系的基因变异情况，为及时准确的临床干预和患者家庭的遗传咨询和生育决策提供了依据。 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 theQDPR 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.
Genetic analysis of eighteen patients from Gansu province with Tetrahydrobiopterin deficiency
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 theQDPR 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.

Tetrahydrobiopterin deficiencyGenetic analysisIntervention treatmentGenetic counselingPedigree

张钏、田芯瑗、王玉佩、马盼盼、陈雪、周秉博、张庆华、郝胜菊、惠玲、殷哲、曹宗富、许芯

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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

国家卫生健康委科学技术研究所，国家人类遗传资源中心，北京　100730

四氢生物蝶呤缺乏症 遗传学分析 干预治疗 遗传咨询 家系

国家十三五重点专项甘肃省科技计划兰州市科技计划国家科技资源共享服务平台项目国家科技资源共享服务平台计划甘肃省出生缺陷与罕见病临床医学研究中心项目甘肃省自然科学基金甘肃省自然科学基金

2016YFC100030722YF7FA0942021-1-1822005DKA21300YCZYPT[2020]05-0321JR7RA68021JR1RA04721JR1RA045

2024

10.3760/cma.j.cn511374-20221028-00727

中华医学遗传学杂志
中华医学会

中华医学遗传学杂志

CSTPCD
影响因子：0.562
ISSN：1003-9406
年,卷(期)：2024.41(2)
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