Clinical profile and molecular characterization of Galactosemia in Brazil: identification of seven novel mutations

BMC Medical Genetics

Research Article

Carolina F. M. Souza¹  Daniel F. Garcia²  Greice A. Molfetta³  Wilson A. Silva³  Carlos E. Steiner⁴  Marlene Turcato⁵  Gilda Porta⁶  José S. Camelo⁷ 

[1] Department of Genetics, Clinical Hospital of the Porto Alegre, Porto Alegre, RS, Brazil;Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil;National Institute of Science and Technology in Stem Cell, and Cell Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil;Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil;National Institute of Science and Technology in Stem Cell, and Cell Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil;Center for Medical Genomics at Clinical Hospital of the Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil;Department of Medical Genetics, School of Medical Science, State University of Campinas, Campinas, SP, Brazil;Department of Neurology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil;Department of Pediatrics, Children’s Institute, Medical School of the University of São Paulo, São Paulo, SP, Brazil;Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil;

关键词: GALT;    Inborn error of galactose metabolism;    Mutation screening;   

DOI  :  10.1186/s12881-016-0300-8

 received in 2015-06-20, accepted in 2016-04-30,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundClassical Galactosemia (CG) is an inborn error of galactose metabolism caused by the deficiency of the galactose-1-phosphate uridyltransferase enzyme. It is transmitted as an autosomal recessive disease and is typically characterized by neonatal galactose intolerance, with complications ranging from neonatal jaundice and liver failure to late complications, such as motor and reproductive dysfunctions. Galactosemia is also heterogeneous from a molecular standpoint, with hundreds of different mutations described in the GALT gene, some of them specific to certain populations, reflecting consequence of founder effect.MethodsThis study reviews the main clinical findings and depicts the spectrum of mutations identified in 19 patients with CG, six with Duarte Galactosemia and one with type 2 Galactosemia in Brazil. Some individuals were diagnosed through expanded newborn screening test, which is not available routinely to all newborns.ResultsThe main classical Galactosemia mutations reported to date were identified in this study, as well as the Duarte variant and seven novel mutations - c.2 T > C (p.M1T), c.97C > A (p.R33S), c.217C > T (p.P73S), c.328 + 1G > A (IVS3 + 1G > A), c.377 + 4A > C (IVS4 + 4A > C), c.287_289delACA (p.N97del) and c.506A > C (p.Q169P). This was expected, given the high miscegenation of the Brazilian population.ConclusionsThis study expands the mutation spectrum in GALT gene and reinforces the importance of early diagnosis and introduction of dietary treatment, what is possible with the introduction of Galactosemia in neonatal screening programs.

【 授权许可】

CC BY   
© Garcia et al. 2016