Mucopolysaccharidosis Type IIID: 12 New Patients and 15 Novel Mutations

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Valstar M. J., Bertoli-Avella A. M., Wessels M. W., Ruijter G. J. G., de Graaf B., Olmer R., ...Daha Fazla

HUMAN MUTATION, cilt.31, sa.5, 2010 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 31 Sayı: 5
  • Basım Tarihi: 2010
  • Doi Numarası: 10.1002/humu.21234
  • Dergi Adı: HUMAN MUTATION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: Sanfilippo syndrome, mucopolysaccharidosis IIID, alpha-N-acetylglucosamine-6-sulphate sulphatase, alpha-N-acetylglucosamine-6-sulphatase, GNS, mutations, SYNDROME TYPE-A, DISEASE TYPE-D, SANFILIPPO-SYNDROME, IDENTIFICATION, GENE, N-ACETYLGLUCOSAMINE-6-SULFATASE, GLYCOSAMINOGLYCANS, HETEROGENEITY, NETHERLANDS, DIAGNOSIS
  • Gazi Üniversitesi Adresli: Evet

Özet

Mucopolysaccharidosis III D (Sanfilippo disease type D, MPS IIID) is a rare autosomal recessive lysosomal storage disorder previously described in only 20 patients. MPS IIID is caused by a deficiency of N-acetylglucosamine-6-sulphate sulphatase (GNS), one of the enzymes required for the degradation of heparan sulphate. So far only seven mutations in the GNS gene have been reported. The clinical phenotype of 12 new MPS IIID patients from 10 families was studied. Mutation analysis of GNS was performed in 16 patients (14 index cases). Clinical signs and symptoms of the MPS IIID patients appeared to be similar to previously described patients with MPS III. Early development was normal with onset of behavioral problems around the age of 4 years, followed by developmental stagnation, deterioration of verbal communication and subsequent deterioration of motor functions. Sequence analysis of the coding regions of the gene encoding GNS (GNS) resulted in the identification of 15 novel mutations: 3 missense mutations, 1 nonsense mutation, 4 splice site mutations, 3 frame shift mutations, 3 large deletions and 1 in-frame small deletion. They include the first missense mutations and a relatively high proportion of large rearrangements, which warrants the inclusion of quantitative techniques in routine mutation screening of the GNS gene. (C) 2010 Wiley-Liss, Inc.