title: Consanguinity and founder effect for Gaucher disease mutation G377S in a population from Tabuleiro do Norte, Northeastern Brazil.
abstract: Gaucher's disease (GD) is caused by a β-glucocerebrosidase deficiency, leading to the accumulation of glucocerebroside in the reticuloendothelial system. The prevalence of GD in Tabuleiro do Norte (TN) (1:4000) is the highest in Brazil. The purpose of this study was to present evidence of consanguinity and founder effect for the G377S mutation (c.1246G>A) among GD patients in TN based on enzyme, molecular and genealogical studies. Between March 2009 and December 2010, 131 subjects at risk for GD (GC in dried blood ≤2.19 nmol/h/ml) and 5 confirmed GD patients from the same community were submitted for molecular analysis to characterize the genetic profile of the population. Based on the enzymatic and molecular analysis, the subjects were classified into three categories: affected (n = 5), carrier (n = 20) and non-carrier (n = 111). All carriers were (G377S/wt). Affected subjects were homozygous (G377S/G377S). The identification of a single mutation in carriers and homozygotes from different generations, the history of the community and the genealogy study suggest that the high prevalence of GD in this population may be due to a combination of consanguinity and founder effect for the G377S mutation.
authors.affiliation: UFRN Postgraduate Program, Natal, Brazil.|Municipal Department of Health, Tabuleiro do Norte, Brazil.
authors.forename: R G
authors.initials: RG
authors.lastname: Chaves
authors.affiliation: Department of Genetics and Evolutionary Biology, USP Institute of Biosciences, São Paulo, Brazil.
authors.forename: L da Veiga
authors.initials: Lda V
authors.lastname: Pereira
authors.affiliation: Department of Genetics and Evolutionary Biology, USP Institute of Biosciences, São Paulo, Brazil.
authors.forename: F T
authors.initials: FT
authors.lastname: de Araújo
authors.affiliation: Department of Genetics and Evolutionary Biology, USP Institute of Biosciences, São Paulo, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Rozenberg
authors.affiliation: UECE Ceará State University, Fortaleza, Brazil.
authors.forename: M D F
authors.initials: MD
authors.lastname: Carvalho
authors.affiliation: UFRGS/ICBS Department of Biochemistry, Porto Alegre, Brazil.
authors.forename: J C
authors.initials: JC
authors.lastname: Coelho
authors.affiliation: UFRGS/HCPA Medical Genetics Service, Porto Alegre, Brazil.
authors.forename: K
authors.initials: K
authors.lastname: Michelin-Tirelli
authors.affiliation: Unichristus School of Medicine, Fortaleza, Brazil.
authors.forename: M de Freitas
authors.initials: Mde F
authors.lastname: Chaves
authors.affiliation: UFRN/CCS Department of Clinical and Toxicological Analysis, Rio Grande do Sul, Brazil.
authors.forename: G B
authors.initials: GB
authors.lastname: Cavalcanti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D005260:Female; D018703:Founder Effect; D005776:Gaucher Disease / Q000235:genetics*; D056726:Genetic Association Studies; D005962:Glucosylceramidase / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree
chemical_list: D005962:Glucosylceramidase
keywords: Gaucher disease; consanguinity; founder effect; genetic testing; mutation