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Limb-Girdle Muscular Dystrophy

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Condition Description  Detection
Indications Specimen Requirements

 

Condition Description                                                                                                                                               

Limb-girdle muscular dystrophy (LGMD) is a descriptive term applied to a clinically and genetically heterogeneous group of childhood- or adult-onset muscular dystrophies. LGMD is characterized by weakness and wasting restricted to the limb musculature, proximal greater than distal. Most individuals with LGMD show relative sparing of the heart and bulbar muscles, although exceptions occur, depending on the genetic subtype. Onset, progression, and distribution of the weakness and wasting vary considerably among individuals and genetic subtypes. Serum creatine kinase (CK) levels in individuals with LGMD are usually elevated, and muscle biopsy reveals dystrophic changes. Immunohistochemistry (IHC) testing of amuscle biopsy sample can be used to determine the presence or absence of specific proteins, and confirmatory genetic testing is available in some cases.

LGMDs are distinct from the much more common X-linked dystrophinopathies, which include Duchenne and Becker muscular dystrophy(DMD/BMD).

Genes                                                                                                                                                                       

ANO5, CAPN3, CAV3, COL6A1, COL6A2, COL6A3, DAG1, DES, DMD, DYSF, EMD, FHL1, FKRP, FKTN, FLNC, GAA, GNE, ISPD, LMNA, MYOT, PLEC, POMGNT1, POMT1, POMT2, SGCA, SGCB, SGCD, SGCG, SMCHD1, SYNE1, TCAP, TRIM32, TTN, VCP

Indications                                                                                                                                                               

This test is indicated for:

Confirmation of a clinical diagnosis of limb-girdle muscular dystrophy(LGMD).

Methodology                                                                                                                                                            

Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient's genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not meant to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient's gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.

 Detection                                                                                                                                                                 

Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions/duplications will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of  the patient's clinical/biochemical phenotype.

Analytical Sensitivity:~99%.

Specimen Requirements                                                                                                                                          

Submit only 1 of the following specimen types

Type: EDTA Whole Blood; Infants (2 years): 3-5 ml; Older Children & Adults: 5-10 ml.

Type: Isolated DNA: In microtainer: (20-30 ug high Quality Genomic DNA, shipped at 2-4 oC). Isolation using the QiagenTM  Puregene kit for DNA extraction is recommended.

Specimen Collection and Shipping: Refrigerate until time of shipment in 100 ng/ul of TE buffer. Ship sample at room temperature with overnight delivery.