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Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations

Marlies J Valstar1, Aida M Bertoli-Avella, Marja W Wessels

  • 1Department of Clinical Genetics, Erasmus University Medical Center, Dr. Molewaterplein 50, Rotterdam, The Netherlands.

Human Mutation
|March 17, 2010
PubMed

Insights

Mucopolysaccharidosis III D (MPS IIID) is a rare genetic disorder. Researchers identified 15 new mutations in the GNS gene, expanding understanding of this lysosomal storage disease.

Area of Science:

  • Genetics
  • Biochemistry
  • Rare Diseases

Background:

  • Mucopolysaccharidosis III D (MPS IIID), also known as Sanfilippo disease type D, is a rare autosomal recessive lysosomal storage disorder.
  • It results from a deficiency in N-acetylglucosamine-6-sulphate sulphatase (GNS), an enzyme crucial for heparan sulphate degradation.
  • Previously, only 20 patients and seven GNS gene mutations were documented.

Purpose of the Study:

  • To investigate the clinical phenotype of new MPS IIID patients.
  • To identify novel mutations in the GNS gene in a cohort of patients with suspected MPS IIID.
  • To characterize the spectrum of genetic alterations in the GNS gene associated with MPS IIID.

Main Methods:

  • Clinical data from 12 new MPS IIID patients from 10 families were collected and analyzed.
  • Mutation analysis of the GNS gene was performed in 16 patients, including 14 index cases.
  • Sequence analysis of the coding regions of the GNS gene was employed to identify mutations.

Main Results:

  • The clinical presentation of the studied MPS IIID patients aligns with previously described cases, characterized by normal early development followed by behavioral issues, developmental stagnation, and progressive decline in communication and motor skills.
  • Sequence analysis identified 15 novel mutations in the GNS gene, including 3 missense, 1 nonsense, 4 splice site, 3 frameshift, 3 large deletions, and 1 in-frame small deletion.
  • These findings include the first reported missense mutations and a significant proportion of large rearrangements in the GNS gene.

Conclusions:

  • The study expands the mutational landscape of MPS IIID by identifying numerous novel GNS gene mutations.
  • The findings highlight the importance of including quantitative techniques for detecting large rearrangements in routine GNS gene mutation screening for MPS IIID.
  • This research contributes to a better understanding of the genetic basis and clinical spectrum of MPS IIID, aiding in diagnosis and potential therapeutic strategies.

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