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.
- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
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.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|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