Confirm suspected laminopathy caused by LMNA mutations including Hutchinson-Gilford progreria, Emery-Dreifuss muscular dystrophy type 2, Limb-girdle muscular dystrophy 1B, Charcot-Marie-Tooth 2B1, Dunnigan type familial partial lipodystrophy, mandibulo-acral dysplasia, atypical Werner syndrome, restrictive dermopathy or dilated cardiomyopathy.
Polymerase Chain Reaction/Sequencing
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 1 mL)
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Background Information for LMNA-Related Disorders (LMNA) Sequencing:
Characteristics of Laminopathies: Mutations in the lamin A/C (LMNA) gene cause a broad range of clinical diseases collectively termed laminopathies. Clinical findings are highly variable.
Hutchinson-Gilford progeria syndrome (HGPS): Accelerated aging, profound failure to thrive, characteristic facies, alopecia, joint degeneration, growth retardation. Average life span is 13 years.
Emery-Dreifuss muscular dystrophy, type 2 (EDMD2): Joint contractures, progressive muscle weakness and wasting, and cardiac disease with conduction defects and arrhythmias.
Familial partial lipodystrophy, Dunnigan type (FLPD): Post-pubescent progressive loss of subcutaneous fat from the extremities and excess fat accumulation on the face and neck.
Mandibuloacral dysplasia (MAD): Post-natal growth retardation, craniofacial and skeletal anomalies, mottled cutaneous pigmentation.
Atypical Werner syndrome (WS): Progeria-like syndrome with features of partial alopecia, premature aging, short stature, hypogonadism, osteoporosis, premature atherosclerosis, weak voice, cataracts.
Restrictive Dermopathy (RD): Skin tightness causes fetal akinesia or hypokinesia deformation sequence; disease is lethal.
Incidence: At least 1 in 8 million for HGPS; DCM occurs in approximately 1 in 2,500 and is familial in 30-60 percent of cases of which approximately 8 percent are caused by LMNA gene mutations; unknown for other LMNA-related conditions.
Inheritance: Laminopathies are inherited as autosomal dominant, recessive, or de novo.
Penetrance: Complete for HGPS; variable for other LMNA-related disorders.
Cause: Pathogenic LMNA gene mutations.
Clinical Sensitivity: Clinical sensitivity is dependant upon the specific LMNA-related disorder.
Methodology: Bidirectional sequencing of the LMNA coding region and intron-exon boundaries.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Some regulatory region mutations, deep intronic mutations, and large deletion/duplications will not be detected.
This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
Laboratory Developed Test (LDT)
|Component Test Code*||Component Chart Name||LOINC|
|2004544||LMNA Sequencing Specimen|
|2004545||LMNA Sequencing Interpretation|
- Atypical Werner Syndrome
- Emery-Dreifuss Muscular Dystrophy Type 2
- Familial Partial Lipodystrophy, Dunnigan Type
- Hutchinson-Gilford Progeria
- LMNA sequencing assay
- Mandibulo-Acral Dysplasia
- Restrictive Dermopathy