The Invitae Comprehensive Mucopolysaccharidoses (MPS) Panel analyzes genes associated with mucopolysaccharidoses. This panel may be appropriate for individuals with signs and symptoms of a mucopolysaccharidosis such as coarse facial features, progressive cognitive disability, inguinal and/or umbilical hernias, hepatosplenomegaly, cardiac valve dysfunction, recurrent ear and respiratory infections, corneal clouding and skeletal deformities. Additionally, this panel may be appropriate for those in whom a MPS condition is suspected due biochemical findings or abnormal newborn screening results. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions.
ARSB GALNS GLB1 GNS GUSB HGSNAT HYAL1 IDS IDUA NAGLU SGSH
AGA CTSA CTSK FUCA1 GNPTAB GNPTG MAN2B1 MANBA MCOLN1 NAGA NEU1 SLC17A5
Phenotypic features of the mucopolysaccharidoses can overlap with certain mucolipidoses and oligosaccharidoses. Given the significant clinical overlap, analyzing the genes associated with these disorders may be appropriate. These genes may be included at no additional charge.
ARSB GALNS GLB1 GNS GUSB HGSNAT HYAL1 IDS IDUA NAGLU SGSH
Phenotypic features of the mucopolysaccharidoses can overlap with certain mucolipidoses and oligosaccharidoses. Given the significant clinical overlap, analyzing the genes associated with these disorders may be appropriate. These genes may be included at no additional charge.
AGA CTSA CTSK FUCA1 GNPTAB GNPTG MAN2B1 MANBA MCOLN1 NAGA NEU1 SLC17A5
The mucopolysaccharidoses are a constellation of diseases caused by the deficiency of a specific lysosomal enzyme involved in the breakdown of complex sugar and protein molecules known as glycosaminoglycans (GAGs, previously called mucopolysaccharides). Specifically, the breakdown of one or more of the following GAGs is disrupted in each MPS: chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS) and/or hyaluronan. Consequently, these substances accumulate in the lysosomes of various tissues resulting in deterioration and degeneration of multiple organs. There is phenotypic variability amongst and within the MPSs, but in general, extensive somatic involvement affecting the heart, lungs, bones, joints and gastrointestinal systems is observed in most MPSs and central nervous system involvement is seen in in types I, II, III and VII. There is a clinical spectrum within each MPS ranging from severe, early onset forms to milder, attenuated forms. Reduced life expectancy is observed in virtually all of the MPSs.
Treatment options, including hematopoietic stem-cell transplant and enzyme replacement therapy, are available for some forms of MPS. Early diagnosis may help slow disease progression and alleviate some symptoms.
Abnormal biochemical studies may include increased urinary GAG levels and reduced enzymatic activity of the enzyme specific to each MPS.
The MPSs are inherited in an autosomal recessive fashion, except for MPSII. MPSII is X-linked.
Collectively the MPSs have an overall incidence of greater than 1:25,000 births.
Individual incidence figures for the different forms of MPS are listed here:
MPS type | Incidence |
---|---|
MPS I | 1:100,00 for the severe form and 1:500,000 in the attenuated form |
MPS II | 1:100,00-1:170,000 male births |
MPS III | 0.3 to 4.1 : 100,000 births (all forms of MPS III) |
MPS IV | MPS IVA 1:71,00 – 179,000 |
MPS1B 1:250,00 – 1,000,000 | |
MPS VI | 1:46,261 births in Turkey to 1:1,505,160 in Sweden |
MPS VII | 1:345,000 – 2,100,000 |
MPS IX | unknown |
This test is appropriate for any individual with any combination of clinical features consistent with a MPS including: coarse facial features, skeletal deformities, progressive mental retardation, inguinal and umbilical hernias, hepatosplenomegaly, recurrent ear and respiratory infections and or corneal clouding.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
Gene | Transcript reference | Sequencing analysis | Deletion/Duplication analysis |
---|---|---|---|
AGA | NM_000027.3 | ||
ARSB | NM_000046.3 | ||
CTSA | NM_000308.3 | ||
CTSK | NM_000396.3 | ||
FUCA1 | NM_000147.4 | ||
GALNS | NM_000512.4 | ||
GLB1 | NM_000404.2 | ||
GNPTAB | NM_024312.4 | ||
GNPTG | NM_032520.4 | ||
GNS | NM_002076.3 | ||
GUSB | NM_000181.3 | ||
HGSNAT | NM_152419.2 | ||
HYAL1 | NM_153281.1 | ||
IDS* | NM_000202.6 | ||
IDUA | NM_000203.4 | ||
MAN2B1 | NM_000528.3 | ||
MANBA | NM_005908.3 | ||
MCOLN1 | NM_020533.2 | ||
NAGA | NM_000262.2 | ||
NAGLU | NM_000263.3 | ||
NEU1 | NM_000434.3 | ||
SGSH | NM_000199.3 | ||
SLC17A5 | NM_012434.4 |
IDS: Detection of complex rearrangements not offered (PMID: 7633410, 20301451).