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Sanfilippo syndrome type D : natural history and identification of 3 novel mutations in the GNS Gene

Authors :
Anna Jansen
Hai Thanh Cao
Frédéric Kaplan
Silver, K.
Leonard, G.
Linda De Meirleir
Willy Lissens
Ingeborg Liebaers
Veilleux, M.
Andermann, M.
Ra Hegele
Andermann, E.
Centre for Medical Genetics
Department of Embryology and Genetics
Pediatrics
Public Health Care
Source :
Anna Jansen, Vrije Universiteit Brussel

Abstract

BACKGROUND: Mucopolysaccharidosis type IIID (MPS-IIID), or Sanfilippo syndrome type D, is a rare autosomal recessive lysosomal storage disorder caused by mutations in the N-acetylglucosamine-6-sulfatase (GNS) gene, leading to impaired degradation of heparan sulfate. OBJECTIVES: To report the natural history of MPS-IIID in 2 siblings described by Kaplan and Wolfe in 1987 and to study the phenotype in 2 other unrelated families with MPS-IIID. Design, Setting, and Patients Case series of 4 patients with MPS-IIID: 2 siblings followed up at the Montreal Neurological Hospital and Institute, 1 patient followed up at the UZ Brussel, and 1 patient recruited through the prenatal counseling program at the UZ Brussel. MAIN OUTCOME MEASURES: Clinical and molecular data collected from 3 families with enzyme-based diagnosis of MPS-IIID. RESULTS: The course of the disease was characteristic of MPS-IIID in all patients, although survival may be longer than was previously reported. In family 1, both siblings were homozygous for a novel nonsense mutation in the GNS gene (c.1168C>T). In family 2, the proband carried a heterozygous mutation occurring in a splice recognition site in the intron 7 boundary (c.876-2A>G). The second mutation in this patient remains to be identified. In family 3, the proband was homozygous for a novel frameshift mutation in GNS due to the insertion of 5 nucleotides (c.1138_1139insGTCCT). CONCLUSIONS: Major issues in the care of patients with MPS-IIID include behavioral problems, sleep problems, recurrent infections, dysphagia, and pain from orthopedic complications. To date, all mutations in GNS predict protein truncation, and there is no obvious genotype-phenotype correlation.

Details

Database :
OpenAIRE
Journal :
Anna Jansen, Vrije Universiteit Brussel
Accession number :
edsair.dedup.wf.001..a682c18c5188965b269a013f5ca6cbae