A community-based study of mucopolysaccharidosis type VI in Brazil: the influence of founder effect, endogamy and consanguinity.

Citation data:

Human heredity, ISSN: 1423-0062, Vol: 77, Issue: 1-4, Page: 189-96

Publication Year:
Usage 11
Abstract Views 10
Link-outs 1
Captures 23
Readers 23
Citations 7
Citation Indexes 7
Repository URL:
Costa-Motta, Fabiana Moura; Bender, Fernanda; Acosta, Angelina; Abé-Sandes, Kiyoko; Machado, Taísa; Bomfim, Thaís; Boa Sorte, Tatiana; da Silva, Danniel; Bittles, Alan; Giugliani, Roberto; Leistner-Segal, Sandra Show More Hide
S. Karger AG
Biochemistry, Genetics and Molecular Biology; Medicine; Consanguinity; Founder effect; Genetic counselling; Mucopolysaccharidosis VI; adolescent; adult; article; Brazil; child; clinical article; consanguineous marriage; consanguinity; endogamy; family history; family size; female; founder effect; gene frequency; gene identification; heterozygote; human; male; Maroteaux Lamy syndrome; missense mutation; pedigree analysis; phenotype; prevalence; rural area; Genetics and Genomics
article description
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.