High-Throughput Sequencing Reveals the Loss-of-Function Mutations in GALT Cause Recessive Classical Galactosemia

Frontiers in Pediatrics

article

Lulu Li¹  Li Ma²  Min Sun²  Jiancheng Jiao²  Yudong Zhang²  Yue Tang¹  Nan Yang¹  Yuanyuan Kong¹ 

[1] Department of Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital;Department of Neonatology, Hebei Provincial Children's Hospital

关键词: classical galactosemia (CG);    high-throughput sequencing;    GATL;    gene mutation;    hepatomegaly;    autosomal recessive (AR);    Chinese patient;    mutation spectrum;   

DOI  :  10.3389/fped.2020.00443

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background: Classical Galactosemia (CG) is a rare autosomal recessive metabolic disease caused by mutations in the galactose-1-phosphate uridyl transferase ( GALT ) gene. This study aim to identify pathogenic mutations underlying classic galactosemia in two Chinese families. Methods: We collected blood samples from two Chinese families and extracted genomic DNA. High-throughput sequencing, sanger sequencing, and bioinformatics analysis were used to investigate the molecular cause of manifestations in the two Chinese families. Results: We found compound heterozygous mutations (c.396C>G; p.His132Gln and c.974C>T; p.Pro325Leu) in family 1 and a homozygous missense variant (c.974C>T; p.Pro325Leu) in family 2. Bioinformatics and Sanger sequencing were performed to verify the identified variants. Conclusion: The present study identified the GALT mutations as a genetic etiology in the two Chinese families with classic galactosemia and expanded the phenotypic and mutational spectrum of GALT . Our findings could be useful in providing evidence for prenatal interventions and more precise pharmacological treatments to patients. High-throughput sequencing conducted in our study is a convenient and useful tool for clinical diagnosis of galactosemia and other associated genetic disorders.

【 授权许可】

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