title: A community-based study of mucopolysaccharidosis type VI in Brazil: the influence of founder effect, endogamy and consanguinity.
abstract: Mucopolysaccharidosis type VI (MPS VI - Maroteaux-Lamy syndrome) is a globally rare lysosomal storage disease caused by a deficiency of arylsulfatase B. However, in Monte Santo, a poor and isolated rural region in Northeast Brazil with large family sizes and high rates of community endogamy and parental consanguinity (α = 0.00483), 9 living and 4 now deceased individuals in 11 kindreds have been diagnosed with MPS VI, all with the same p.H178L missense founder mutation. A further 33 deceased persons have been identified by family members as exhibiting the disease phenotype. Detailed pedigrees were constructed for the 13 genomically confirmed MPS VI patients, with blood samples collected from 236 unaffected family members to determine the prevalence of the p.H178L mutation. A total of 98 (20.8%) mutant alleles and 374 (79.2%) normal alleles were identified, with 41.5% of the individuals heterozygous for the p.H178L mutation and 58.5% homozygous for the normal allele. A significant number of other family members with a 50 or 25% chance of being heterozygous for the p.H178L mutation were unavailable for testing. The data indicate a compelling case for community-based neonatal screening in conjunction with further initiatives among MPS VI family members to promote genetic education and genetic counselling.
authors: Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors: Fabiana Moura
authors: FM
authors: Costa-Motta
authors: Fernanda
authors: F
authors: Bender
authors: Angelina
authors: A
authors: Acosta
authors: Kiyoko
authors: K
authors: Abé-Sandes
authors: Taísa
authors: T
authors: Machado
authors: Thaís
authors: T
authors: Bomfim
authors: Tatiana
authors: T
authors: Boa Sorte
authors: Danniel
authors: D
authors: da Silva
authors: Alan
authors: A
authors: Bittles
authors: Roberto
authors: R
authors: Giugliani
authors: Sandra
authors: S
authors: Leistner-Segal
mesh_terms: D001938:Brazil / Q000453:epidemiology; D003241:Consanguinity; D004252:DNA Mutational Analysis; D018703:Founder Effect; D005817:Genetic Counseling / Q000379:methods; D005828:Genetics, Population; D006801:Humans; D008393:Marriage / Q000706:statistics & numerical data*; D009087:Mucopolysaccharidosis VI / Q000453:epidemiology* / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D015995:Prevalence