Molecular characterization of MPS IIIA, MPS IIIB in Iranian patients

Mucopolysaccharidosis III (MPS III), also known as Sanfilippo syndrome belongs to a group of lysosomal storage diseases(LSD ) , is an autosomal recessive disorder. MPS III caused by an impairment of degradation of heparan sulfate, one of glycosaminoglycans (GAGs).The patients present with tissue heparan sulphate accumulation and abnormal excretion in urine. This syndrome is characterized by severe, early and progressive central nervous system degeneration with mildsomatic involvement. Onset of clinical features usually occurs between 2 and 6 years of age, with behavioural disturbances(aggressiveness, hyperactivity, insomnia), psychomotor delay and poor speech development .Most patients die of end-stageneurodegenerative disease by the end of the second decade. Birth prevalences of 0.28 to 4.1 per 100,000 have been reported. MPS III includes 4 subtypes, types A to D, each of which results from a specific impaired lysosomal enzyme. MPS-IIIA and MPS-IIIB involve deficiencies of heparan sulfate sulfamidase (SGSH) and α -N-acetylglucosaminidase (NAGLU),respectively. In this study, screening of SGSH and NAGLU genes using PCR -sequencing analysis on genomic DNA fragments was performed in three Iranian patients with MPS IIIA and tow with MPS IIIB.These approaches allowed the identification of 3 missense mutations, including c.364G>A and c.448C>T homozygous mutations in the SGSH gene , and c.2045T>G homozygous mutation in the NAGLU gene.

کلیدواژه ها:

Sanfilippo syndrome ، MPS-IIIA ، MPS-IIIB ، SGSH ، NAGLU