Test code: 4298

GM1 Gangliosidosis: GLB1 Gene Deletion/Duplication
Test code: 4298
Turnaround time: 3 weeks

CONDITION DESCRIPTION

GM1-gangliosidosis and Morquio B disease are both rare autosomal recessive lysosomal storage disorders caused by a deficiency of the enzyme beta-galactosidase (GLB1; E.C.3.2.1.23) due to mutations in the GLB1 gene. The enzyme has a catalytic effect on the ganglioside GM1, keratan sulfate, and glycopeptides, and the enzyme is absent or reduced in GM1-gangliosidosis and Morquio B patients. Morquio B patients show reduced catalytic activity for keratan sulfate and oligosaccharides but normal activity for ganglioside GM1. Ganglioside GM1 is mainly stored in neuronal tissue, while keratan sulfate mainly accumulates in cartilage. GM1-gangliosidosis has been classified into three major clinical forms according to age of onset and severity of symptoms: type I (infantile), type II (late infantile/juvenile) and type III (adult) [Suzuki et al., 2001]. Type I is the most severe and is associated with developmental arrest observed within 3 to 6 months of birth, macular cherry-red spots, skeletal dysplasia and death usually within the first two years of life.

Morquio B disease or mucopolysaccharidosis type IVB (MPS IVB) is characterized by progressive, generalized skeletal dysplasia without central nervous system involvement and no clinical signs of storage disease in neuronal tissues.

More than 50 disease-causing mutations and several polymorphisms have been described in the GLB1 gene. There are very few mutational studies in specific populations, such as those of patients from Italy [Caciotti et al., 2003; Morrone et al., 2000] or Brazil [Silva et al., 1999]. Furthermore, less than 30 Morquio B patients worldwide have been characterized for their DNA mutations [Bagshaw et al., 2002; Paschke et al., 2001]. Diagnostic sequencing analysis of the GLB1 gene coding region is available for GM1 patients and their at-risk relatives on a clinical basis.

References:
1. Silva CM, et al. 1999. Six novel beta-galactosidase gene mutations in Brazilian patients with GM1-gangliosidosis. Hum Mutat 13:401-9.
2. Santamaria R et al. Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies. Hum Mutat. 2006 Oct; 27(10):1060.

GENES
GBL1

INDICATIONS
• Confirmation of clinical diagnosis of GM1.
• Prenatal testing for known familial mutation(s).
• Assessment of carriers 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 be 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 CEN4GEn) 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.

RELATED TESTS
• Known mutation analysis (Custom Diagnostics) is available to test family members.