title: Identification and characterisation of an 8.7 kb deletion and a novel nonsense mutation in two Italian families with Sanfilippo syndrome type D (mucopolysaccharidosis IIID).
abstract: Sanfilippo syndrome type D is an autosomal recessive lysosomal storage disease that is caused by a deficiency of N-acetylglucosamine-6-sulphatase, one of the enzymes involved in the catabolism of heparan sulphate. Only 15 patients have been described in the literature and just two mutations have been reported to date. We present the clinical, biochemical and molecular analysis of two Italian Sanfilippo D families. Novel homozygous mutations were identified in the affected patients from each family: a large intragenic deletion of 8723 bp encompassing exons 2 and 3 in family 1 and a nonsense mutation, Q272X, in family 2. The deletion is the first large intragenic deletion to be reported in any of the four Sanfilippo subtypes, including Sanfilippo type C in which the gene has recently been identified.
authors.affiliation: Biochemistry, Endocrinology and Metabolism Unit, UCL Institute of Child Health, London, UK. C.Beesley@ich.ucl.ac.uk
authors.forename: Clare E
authors.initials: CE
authors.lastname: Beesley
authors.forename: Daniela
authors.initials: D
authors.lastname: Concolino
authors.forename: Mirella
authors.initials: M
authors.lastname: Filocamo
authors.forename: Bryan G
authors.initials: BG
authors.lastname: Winchester
authors.forename: Pietro
authors.initials: P
authors.lastname: Strisciuglio
mesh_terms: D001483:Base Sequence; D002648:Child; D018389:Codon, Nonsense; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D007558:Italy; D008297:Male; D009084:Mucopolysaccharidosis III / Q000201:enzymology* / Q000235:genetics* / Q000652:urine; D017384:Sequence Deletion; D013429:Sulfatases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; D006025:Glycosaminoglycans; D013429:Sulfatases; C018719:N-acetylglucosamine-6-sulfatase