Molecular Characterization of Galactosemia: Identification of Six Novel GALT Gene Mutations

Abstract

Background: Classic galactosemia (CG) is an inborn error of galactose metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT). This enzyme causes the conversion of uridine diphosphate- glucose (UDP)-glucose and galactose-1-phosphate (Gal-1-P) to glucose-1-phosphate and UDP-galactose. The absence of this enzyme results in the accumulation of the metabolites galactitol and Gal-1-P. The CG is heterogeneous at clinical and molecular levels. Objectives: This study provides some data for the investigation of the introduction of new mutations of the GALT gene that involved the cause of galactosemia in the Iranian population. Methods: In this cross-sectional study, 31 newborns diagnosed with galactosemia were investigated for the mutations of the GALT gene in Tehran province, Iran, from March 2014 to December 2019. The polymerase chain reaction sequencing method was used to analyze the GALT gene. Results: The sequence results showed 11 pathogenic mutations on the GALT gene, including five mutations in exon 10, two mutations in exon 9, two mutations in exon 5, one mutation in exon 6, and one mutation in exon 7. Moreover, six new mutations of the GALT gene were identified in the Iranian population, namely c.442C>T (R148W), c.881T>A (F294Y), c.997C>T (R333W), c.940A>G (N314D), c.1030C>A (Q344K), and c.1018G>A (E340K). Other mutations identified in this study were c.563A>G (Q188R), c.855G>T (K285N), c.626A>C (Y209S), c.404C>T (S135L), and c.958G>A (A320T). The most common mutations in this study were p.Q188R (51.6%), K285N (9.67%), E340K (9.67%), and R148W (6.45%). Conclusions: This study identified 11 different pathogenic mutations of the GALT gene in the Iranian population with galactosemia. The identification of the mutations involved in the development of CG in the Iranian population can play an important role in early diagnosis and intervention. The GALT gene mutations identified in this study can be used as screening markers to identify Iranian children with CG.