Sanfilippo syndrome in Turkey: Identification of novel mutations in subtypes A and B.

Sanfilippo syndrome (mucopolysaccharidosis type III, MPS III) is a progressive disorder in which patients are characterized by severe central nervous system degeneration together with mild somatic disease. MPS III results from a deficiency in one of the four enzymes involved in the degradation of heparan sulfate, with sulfamidase (SGSH) being deficient in MPS IIIA and a-N-acetylglucosaminidase (NAGLU) deficient in MPS IIIB. Mutation screening using SSCP/heteroduplex analysis on genomic DNA fragments was performed in five Turkish MPS IIIA and eight Turkish MPS IIIB patients. In this study two mutations of SGSH were identified in MPS IIIA patients: R74C and the novel mutation P288S, and one polymorphism (IVS1+23 C>G). Five different mutations of NAGLU were identified in MPS IIIB patients: L682R, H248R, E153K, g.17703 A>G (novel), and T437I (novel). The clinical data of all patients are reported in detail. A high degree of genetic heterogeneity was observed in the Turkish MPS IIIA and MPS IIIB patients.