Founder mutation R245H of Sanfilippo syndrome type A in the Cayman Islands.
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.
Rady
Peter L
PL
Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Surendran
Sankar
S
Vu
Ahn T
AT
Hawkins
Judy C
JC
Michals-Matalon
Kimberlee
K
Tyring
Stephan K
SK
Merren
Joy
J
Kumar
Alla K
AK
Matalon
Reuben
R
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
D006867:Hydrolases; C022708:N-sulfoglucosamine sulfohydrolase