Mucopolysaccharidosis Type IIID: GNS Gene Deletion/Duplication

Condition Description

Mucopolysaccharidosis type IIID (MPS IIID, Sanfilippo syndrome type D) is a member of a group of inherited metabolic disorders collectively termed mucopolysaccharidoses (MPSs). The MPSs are caused by a deficiency of lysosomal enzymes required for the degradation of mucopolysaccharides or glycosaminoglycans (GAGs) within the lysosome. When functioning normally, the lysosomal enzymes break down these GAGs, however when the enzyme is deficient, the GAGs build up in the lysosomes causing damage to the bodys tissues. The MPSs share a chronic progressive course with multisystem involvement, characteristic physical features, laboratory findings, and radiographic abnormalities.

MPS IIID is an autosomal recessive disorder caused by a deficiency of the N-acetylglucosamine 6-sulfatase (GNS) enzyme and build up of heparin sulfate. Clinical features of MPS IIID include hyperactivity, aggressiveness, and developmental delays. Mental abilities decline as the disease progresses. Involvement of other organ systems tends to be mild and dysmorphic features are subtle than those observed in other types of mucopolysaccharidosis [1]. MPS IIID is caused by mutations in the GNS gene, but the disorder is clinically indistinguishable from MPS IIIA, MPS IIIB, and MPS IIIC, which are caused by mutations in other genes. All four forms of MPS III result in buildup of the same GAG, heparin sulfate. Diagnostic sequencing analysis of the GNS gene coding region is available for MPS type IIID patients and their at-risk relatives on a clinical basis.

For questions about testing for MPS IIID, call EGL Genetics at 470-378-2200. For further clinical information about lysosomal storage diseases, including management and treatment, call the Emory Lysosomal Storage Disease Center at (404) 778-8565 or (800) 200-1524.

Visit www.ThinkGenetic.com for patient-friendly information on mucopolysaccharidosis type III.

References:
1). Muenzer, J., The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr, 2004. 144(5 Suppl): p. S27-34.
2). Beesley, C.E., D. Burke, M. Jackson, A. Vellodi, B.G. Winchester, and E.P. Young, Sanfilippo syndrome type D: identification of the first mutation in the N-acetylglucosamine-6-sulphatase gene. J Med Genet, 2003. 40(3): p. 192-4.
3). Beesley, C.E., D. Concolino, M. Filocamo, B.G. Winchester, and P. Strisciuglio, Identification and characterisation of an 8.7kb deletion and a novel nonsense mutation in two Italian families with Sanfilippo syndrome type D (mucopolysaccharidosis IIID). Mol Genet Metab, 2006.
4). Mok, A., H. Cao, and R.A. Hegele, Genomic basis of mucopolysaccharidosis type IIID (MIM 252940) revealed by sequencing of GNS encoding N-acetylglucosamine-6-sulfatase. Genomics, 2003. 81(1): p. 1-5

Genes (1)

Indications

  • Confirmation of a clinical diagnosis of MPS IIID
  • Prenatal testing for known familial mutations.
  • Assessment of carrier status in high risk family members known mutation analysis.

Methodology

DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.

Detection

Detection is limited to duplications and deletions. Array CGH will not detect point mutations or intronic mutations. Results of molecular analysis must interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

When sample fails to meet the acceptable criteria, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
DNA, Isolated
DNA

Requirements
Microtainer
3µg
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.
Whole Blood (EDTA)
WBP

Requirements
EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 24 hours of collection. Do not refrigerate or freeze.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample. Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside EGL Genetics, please submit a copy of the sequencing report with the test requisition. Contact the laboratory if further information is needed.
  • Mucopolysaccharide screen (urine GAG) (GA)
  • Gene Sequencing for MPS IIIA (AW) and MPS IIIB (BB)
  • Known mutation analysis (Custom Diagnostics) is available to test family members.
  • Prenatal testing is available for known familial mutations only. Please call the Laboratory Genetic Counselor for specific requirements for prenatal testing before collecting a fetal sample.

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