The Genetic Basis of Galactosemia in Iranian Patients: Identification of Twenty Novel Mutations in GALT, GALK1 and GALE Gene

Abstract

Abstract Introduction: Galactosemia is a metabolic disorders that affects newborns. The enzyme deficiency of GALT, GALK and GALE are implicated with galactose metabolic disorders. The aim of this study is identify the profile mutations of GALT, GALK1 and GALEgene in the Iranian patients with galactosemia. Method and materials: In this study, 93 patients who have the diagnosis of galactosemia were investigated for mutation of the GALT, GALK1 and GALE gene. Genomic DNA was extracted from peripheral blood via kit and the PCR–Sequencing method was used to identify mutation of the GALT, GALK1 and GALE gene. Results: DNA Sequencing analysis identified 9 novel different mutations on the GALT gene, including: five missense mutations p.M177V (3/22%), R204Q (2/69%), L218V (2/15%), T268N (2/15%) and A379T (2/15%) and also, four synonymous mutations c.498T>A, c.876G>A, c.945T>C and c.1128A>T with 0/53% frequency. The most common mutations of GALTgene was p.Q188R (37/7%), K285N (4/9%) and R148W (4/3%). We detected 8 new different mutations on the GALK1 gene, including six missense mutations p.A198V (6/44%), R287C (2/15%), K217R (2/15%), E284D (2/69%), R228H (2/15%) and A387T (2/15%) two synonymous mutations c.840 C›T and c.1152C>T with 0/53% frequency. Also, in this study we identified 3 new synonymous mutations on the GALE gene including: c.957G›A (1/07%), c.879G›C (0/53%) and c.285C>T (1/07%). Conclusion: Identification of mutations involved in the development of galactosemia and designing a suitable diagnostic panel based on the detected mutations in GALT, GALK1 and GALE genes, can play an important role in neonatal screening program and early diagnosis.