#ExistInterpData>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.
Limb-girdle muscular dystrophy, type1B (LGMD1B): Progressive proximal lower limb weakness and atrioventricular cardiac conduction complications.
Charcot-Marie-Tooth, type 2B1 (CMT2B1): Symmetrical distal muscle weakness and atrophy, depressed or absent tendon reflexes.
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.
Dilated cardiomyopathy (DCM): Progressive ventricular dilation and impaired systolic function leading to congestive heart failure.
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: Rare diagnostic errors can occur due to primer site mutations. 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 at www.aruplab.com.
See Compliance Statement C: www.aruplab.com/CS
||Atypical Werner Syndrome (LMNA-Related Disorders (LMNA) Sequencing)
, Dilated Cardiomyopathy (LMNA-Related Disorders (LMNA) Sequencing)
, Emery-Dreifuss Muscular Dystrophy Type 2 (LMNA-Related Disorders (LMNA) Sequencing)
, Familial Partial Lipodystrophy, Dunnigan Type (LMNA-Related Disorders (LMNA) Sequencing)
, Hutchinson-Gilford Progeria (LMNA-Related Disorders (LMNA) Sequencing)
, Laminopathies (LMNA-Related Disorders (LMNA) Sequencing)
, Limb Girdle Muscular Dystrophy 1B (LMNA-Related Disorders (LMNA) Sequencing)
, Mandibulo-Acral Dysplasia (LMNA-Related Disorders (LMNA) Sequencing)
, Restrictive Dermopathy (LMNA-Related Disorders (LMNA) Sequencing)