title: Founder mutation R245H of Sanfilippo syndrome type A in the Cayman Islands.
abstract: Sanfilippo A syndrome is an autosomal recessive lysosomal storage disease. This disease was reported in the Cayman Islands population with carrier frequency of 1/7 to 1/10 in the West Bay district of Grand Cayman. The carrier testing of Sanfilippo A disease for families at risk was carried out using the thermal characteristics of sulfamidase activity. In the present study, a search for mutations in the sulfamidase gene in an index family was performed. In addition, 77 individuals, relatives of children with Sanfilippo A syndrome, were also studied by single-strand conformation polymorphism (SSCP), restriction fragment-length polymorphism (RFLP) analyses, and sequencing. A single mutation, G746A (R245H), was found in the family, with the patient being homozygous and both parents and 1 of the 3 siblings being carriers. Among the 77 family members of the patient with Sanfilippo syndrome, the same mutation was found among carriers of the disease. The finding of a single mutation supports the idea of a founder effect, which facilitates accurate carrier identification of Sanfilippo A syndrome in the population of Cayman Islands.
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Rady
authors.forename: Sankar
authors.initials: S
authors.lastname: Surendran
authors.forename: Ahn T
authors.initials: AT
authors.lastname: Vu
authors.forename: Judy C
authors.initials: JC
authors.lastname: Hawkins
authors.forename: Kimberlee
authors.initials: K
authors.lastname: Michals-Matalon
authors.forename: Stephan K
authors.initials: SK
authors.lastname: Tyring
authors.forename: Joy
authors.initials: J
authors.lastname: Merren
authors.forename: Alla K
authors.initials: AK
authors.lastname: Kumar
authors.forename: Reuben
authors.initials: R
authors.lastname: Matalon
mesh_terms: D019943:Amino Acid Substitution; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D006579:Heterozygote; D006801:Humans; D006867:Hydrolases / Q000235:genetics; D008297:Male; D009084:Mucopolysaccharidosis III / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D014900:West Indies
chemical_list: D006867:Hydrolases; C022708:N-sulfoglucosamine sulfohydrolase