Ordering Recommendation

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.

Mnemonic
LMNA FGS
Methodology

Polymerase Chain Reaction/Sequencing

Performed

Varies

Reported

14-21 days

New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
Specimen Required
Patient Preparation
Collect

Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 1 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable

Reference Interval
Interpretive Data

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.

Compliance Category

Laboratory Developed Test (LDT)

Note
Hotline History
N/A
CPT Codes

81406

Components
Component Test Code* Component Chart Name LOINC
2004544 LMNA Sequencing Specimen
2004545 LMNA Sequencing Interpretation
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • Atypical Werner Syndrome
  • Emery-Dreifuss Muscular Dystrophy Type 2
  • Familial Partial Lipodystrophy, Dunnigan Type
  • Hutchinson-Gilford Progeria
  • Laminopathies
  • LMNA sequencing assay
  • Mandibulo-Acral Dysplasia
  • Restrictive Dermopathy
LMNA-Related Disorders (LMNA) Sequencing