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

Classical Galactosemia (CG) is a rare autosomal recessive metabolic disease caused by mutations in the galactose-1-phosphate uridyl transferase () gene. This study aim to identify pathogenic mutations underlying classic galactosemia in two Chinese families. 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. 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. The present study identified the mutations as a genetic etiology in the two Chinese families with classic galactosemia and expanded the phenotypic and mutational spectrum of . 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.