PMC Limb-Girdle Muscular Dystrophy Panel

Associated Conditions
- Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps
- Anterior segment dysgenesis with cerebral involvement
- Bardet-Biedl syndrome, Muscular dystrophy, limb-girdle
- Becker muscular dystrophy
- Brain small vessel disease
- Cataract 16, multiple types
- Cataract, myofibrillar myopathy and cardiomyopathy
- Central core disease
- Centronuclear myopathy
- Centronuclear myopathy 5
- Childhood-onset proximal spinal muscular atrophy with contractures
- Congenital cataract and cardiomyopathy
- Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A, 12
- Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type C, 12
- Creatine phosphokinase, elevated serum
- Dilated cardiomyopathy (DCM)
- Dowling-Degos disease 4
- Duchenne muscular dystrophy
- Emery-Dreiffus muscular dystrophy
- Facioscapulohumeral muscular dystrophy
- Facioscapulohumeral muscular dystrophy, type 2
- Glycogen storage disease
- Gnathodiaphyseal dysplasia, LGMD2L and distal MMD3 muscular dystrophies
- Heart-hand syndrome
- Hemorrhage, intracerebral
- Hereditary myopathy with early respiratory failure
- Hypertrophic cardiomyopathy (HCM)
- Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism
- Limb-girdle muscular dystrophy
- Lipodystrophy (Dunnigan)
- Long QT syndrome, Tateyama type
- Malignant hyperthermia
- Malouf syndrome
- Mandibuloacral dysplasia type A
- Microcephaly, seizures, and developmental delay
- Minicore myopathy
- Minicore myopathy with external ophthalmoplegia
- Miyoshi muscular dystrophy,
- Multicore myopathy
- Muscle-eye brain disease
- Muscular dystrophy with progressive weakness, distal contractures and rigid spine
- Muscular dystrophy, congenital merosin-deficient
- Muscular dystrophy, congenital, due to integrin alpha-7 deficiency
- Muscular dystrophy, congenital, LMNA-related
- Muscular dystrophy, congenital, megaconial
- Muscular dystrophy, congenital, with cataracts and intellectual disability (MDCCAID)
- Muscular dystrophy, limb-girdle
- Muscular dystrophy, limb-girdle, type 2J
- Muscular dystrophy, limb-girdle, type 2Z
- Muscular dystrophy, limb-girdle, type IC
- Muscular dystrophy, rigid spine
- Muscular dystrophy-dystroglycanopathy
- Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies)
- Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8
- Muscular dystrophy-dystroglycanopathy (limb-girdle)
- Myopathy, congenital, with fiber- disproportion
- Myopathy, congenital, with neuropathy and deafness
- Myopathy, distal
- Myopathy, distal, with anterior tibial onset
- Myopathy, early-onset, areflexia, respiratory distress, and dysphagia
- Myopathy, early-onset, with fatal cardiomyopathy (Salih myopathy)
- Myopathy, mitochondrial, and ataxia
- Myopathy, myofibrillar
- Myopathy, myofibrillar 8
- Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related
- Myopathy, myofibrillar, Muscular dystrophy, limb-girdle, 1A
- Myopathy, myosin storage
- Myopathy, spheroid body
- Myopathy, X-linked, with excessive autophagy
- Neutral lipid storage disease with myopathy
- Porencephaly
- Progeria Hutchinson-Gilford type
- Retinal artery tortuosity
- Rippling muscle disease 2
- Scapuloperoneal syndrome, neurogenic, Kaeser type
- Schizencephaly
- Slovenian
- Spinocerebellar ataxia, autosomal recessive 8
- Tibial muscular dystrophy
- Walker-Warburg syndrome

Methodology

Targeted Exome/ Slice Exome (Next Generation Sequencing including Copy Number Variation)

Coverage

120x

Assay Information
- CAPN3: Deletion/duplication analysis is not offered for exon 24.
- DMD: Analysis guarantees del/dup detection at single-exon resolution.
- FKTN: Analysis includes the intronic variant NM_001079802.1:c.647+2084G>T (also known as NM_001079802.1:c.648-1243G>T) and the ~3 kb retrotransposon insertion in the 3' UTR at position NM_001079802‚Äã.1:c.*4392_*4393.
- GAA: Analysis includes the promoter variant NM_000152.3:c.-32-13T>G as well as the common exon 18 deletion.
- TTN: Exons 45-46| 147| 149| 164| 172-201 (NM_001267550.2) are excluded from analysis. TTN variants are included in the primary report based on functional effect and/or location. A complete list of variants of uncertain significance| likely benign and benign variants in TTN is available upon request. Variants are named relative to the NM_001267550.2 (meta) transcript. Variants in the coding sequence and intronic boundaries of the clinically relevant NM_133378.4 (N2A) and fetal isoforms are reported (PMID: 25589632| 29598826| 29691892| 31660661)| with the exception of the PEVK tandem repeat region (172-198) (PMID: 28040389).

Ordering information

Turnaround Time: 10 business days

Preferred Speciment: Saliva Kits (available upon request)

Alternate Specimens: Nail clippings or 3-mL whole blood in purple top EDTA tube

Request a specimen collection kit

Limitations

All sequencing technologies have limitations. A negative result from this analysis does not rule out a possible genetic diagnosis as some variants may not be detected by this test. This test is not designed to detect low level mosaicism, structural rearrangements, indels >40bp, deep intronic variants of unknown clinical significance, or large cytogenetic CNVs. Certain inherent qualities of the human genome, for example repetitive regions/homopolymers, GC rich, pseudogenes, and rare polymorphisms, pose significant technical challenges such as sequence misalignment that may potentially impact the accuracy of the results. False negative results may also occur in the setting of allogeneic bone marrow, stem cell transplantation, active or chronic hematologic conditions, recent blood transfusions, suboptimal DNA quality or PCR trace contamination. Other potential sources of error include sample mix-ups and clerical issues.

References
- 1. Richards S et al. Genetics in medicine. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 2015 May;17(5):405-24 (PMID: 25741868)
- 2. GnomAD (gnomAD)
- 3. CSPEC (ClinGen variant classification rules registry) Criteria Specification Registry
- 4. Normal copy number variation in healthy individuals database of genomic variants: http://dgv.tcag.ca/dgv/app/home
- 5. Riggs, E.R., Andersen, E.F., Cherry, A.M. et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med 22, 245–257 (2020). https://doi.org/10.1038/s41436-019-0686-8
- 6. Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014 Jan 1;42(1):D980-5. doi: 10.1093/nar/gkt1113. PubMed PMID: 24234437.
- 7. Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), Copyright® 1966-2012. World Wide Web URL: http://omim.org.
- 8. http://tinyurl.com/ACMGv4 (ACMG/ Clingen draft Interpretation SOP); clingen_variant-curation_sopv1.pdf

Order a Kit:

New Provider:

Contact:

Test Description

Associated Conditions

Methodology

Coverage

Assay Information

Ordering information

Limitations

References

Tagged Genes