Mucopolysaccharidosis Type VII: GUSB Gene Deletion/Duplication

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Condition Description

Mucopolysaccharidosis type VII (MPS VII) 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 also called glycosaminoglycans (GAGs) within the lysosome. When functioning normally, the lysosomal enzymes break down these GAGs, however when the enzyme is deficient, the GAG build up in the lysosomes causing damage to the bodys tissues. The MPSs share a chronic progressive course with multisystem involvement, several physical features, laboratory findings, and radiographic abnormalities; these include facial coarsening, hepatomegaly, excretion of urinary GAG fragments, and leukocyte inclusion bodies.

Mucopolysaccharidosis type VII (MPS VII) is an autosomal recessive that occurs when certain mucopolysaccharides, specifically dermatan, heparan, and chondroitin sulfates accumulate in lysosomes due to a deficiency of the enzyme beta-glucuronidase. Unlike other lysosomal storage disorders in which patients begin life with a period of normal development, patients with MPS VII have a high incidence of hydrops fetalis [1]. Clinical features of MPS VII vary widely between patients and include short stature, course facial features, hepatosplenomegaly, respiratory difficulties, hearing loss, and mental retardation.

Mutations in the GUSB gene cause deficiency of beta-glucuronidase leading to MPS VII. A pseudodeficiency allele, a mutation that reduce enzyme activity but does not cause disease, has been described [2] and will be detected by this sequencing analysis. Diagnostic sequencing analysis of the GUSB gene coding region is available for MPS type VII patients and their at-risk relatives on a clinical basis.

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.

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). Vervoort, R., M.R. Islam, W. Sly, A. Chabas, R. Wevers, J. de Jong, I. Liebaers, and W. Lissens, A pseudodeficiency allele (D152N) of the human beta-glucuronidase gene. Am J Hum Genet, 1995. 57(4): p. 798-804.
3). Vervoort, R., N.R. Buist, W.J. Kleijer, R. Wevers, J.P. Fryns, I. Liebaers, and W. Lissens, Molecular analysis of the beta-glucuronidase gene: novel mutations in mucopolysaccharidosis type VII and heterogeneity of the polyadenylation region. Hum Genet, 1997. 99(4): p. 462-8.
4). Yamada, S., S. Tomatsu, W.S. Sly, R. Islam, D.A. Wenger, S. Fukuda, K. Sukegawa, and T. Orii, Four novel mutations in mucopolysaccharidosis type VII including a unique base substitution in exon 10 of the beta-glucuronidase gene that creates a novel 5'-splice site. Hum Mol Genet, 1995. 4(4): p. 651-5.
5). Vervoort, R., M.R. Islam, W.S. Sly, M.T. Zabot, W.J. Kleijer, A. Chabas, A. Fensom, E.P. Young, I. Liebaers, and W. Lissens, Molecular analysis of patients with beta-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII. Am J Hum Genet, 1996. 58(3): p. 457-71.

Genes (1)

Indications

  • Confirmation of a clinical diagnosis of MPS VII
  • 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.

Please note that a "backbone" of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off-target copy number variants causative of disease may be identified that may or may not be related to the patient's phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.

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

Submit only 1 of the following specimen types

Preferred specimen type: Whole Blood

Type: Whole Blood

Specimen Requirements:

In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva

Specimen Requirements:

OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

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 of Emory Genetics Laboratory, 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)
  • Lysosomal enzyme screening panel (LS)
  • 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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