Table 1.
Human pathologies related to mutations in genes coding for nuclear lamina components
Human pathology | OMIM* | Major phenotypes | Mutated gene | Key references |
Autosomal dominant Emery-Dreifuss muscular dystrophy | #181350 | Early joint contractures, slowly progressive muscle weakness and wasting and cardiac involvement | LMNA, encoding lamins A and C | Bonne 1999; Bonne 2000 |
Autosomal recessive Emery-Dreifuss muscular dystrophy | #604929 | Early joint contractures, slowly progressive muscle weakness and wasting and cardiac involvement | LMNA, encoding lamins A and C | Bonne 2000 |
Autosomal dominant limb girdle muscular dystrophy 1B | #159001 | Progressive muscle weakness affecting both upper arms and legs | LMNA, encoding lamins A and C | Muchir 2000 |
Autosomal dominant dilated cardiomyopathy with conduction system defect 1A | #115200 | Conduction system defects including sinus bradycardia, atrioventricular conduction block, or atrial arrhythmias. Variable skeletal muscle involvement. | LMNA, encoding lamins A and C | Fatkin 1999 |
Autosomal recessive Charcot-Marie-Tooth disorder type 2B1 | #605588 | Axonal peripheral neuropathy characterized by distal muscle weakness and atrophy, mild sensory loss and normal or near-normal nerve conduction velocities | LMNA, encoding lamins A and C | De Sandre-Giovanni 2002 |
Autosomal dominant Dunnigan-type familial partial lypodystrophy | #151660 | Loss of subcutaneous fat in the lower limbs and the gluteal region. Increase in subcutaneous fat in the face, neck and upper trunk. Insulin resistance and related metabolic complications, such as glucose intolerance, diabetes, dyslipidemia and hepatic steatosis. | LMNA, encoding lamins A and C | Cao and Hegele 2000; Shackleton 2000 |
Autosomal dominant lipoatrophy with diabetes, hepatic steatosis, hypertrophic cardiomyopathy and leukemelanodermic papules | #608056 | Acquired lipoatrophy with insulin-resistant diabetes, hypertriglyceridemia, hepatic steatosis, hypertrophic cardiomyopathy with valvular involvement and disseminated whitish papules | LMNA, encoding lamins A and C | Caux 2003 |
Autosomal recessive mandibuloacral dysplasia | #248370 | Postnatal growth retardation, craniofacial anomalies, skeletal malformations and mottled cutaneous pigmentation | LMNA, encoding lamins A and C | Novelli 2002 |
Autosomal dominant Hutchinson-Gilford progeria syndrome | #176670 | Short stature, alopecia, absence of subcutaneous fat, stiffness of joints, bone changes, musculosketal abnormalities, diabetes type II, severe atherosclerosis | LMNA, encoding lamins A and C | Eriksson 2003; De Sandre-Giovanni 2003 |
Autosomal dominant atypical Werners's syndrome | #277700 | Loss and graying of hair, hoarseness, and scleroderma-like skin changes, followed by bilateral ocular cataracts, type 2 diabetes mellitus, hypogonadism, skin ulcers and osteoporosis | LMNA, encoding lamins A and C | Chen 2003 |
Autosomal dominant restrictive dermopathy lethal | #275210 | Intrauterine growth retardation, tight and rigid skin with prominent superficial vessels, bone mineralization defects, dysplastic clavicles, arthrogryposis and early neonatal death | LMNA, encoding lamins A and C | Navarro 2004 |
LMNA-related congenital muscular dystrophy | Myopathy phenotype detected as early as 1 y of age. Much more rapid course than eDMD. Deficit of head support or axial muscle weakness. | LMNA, encoding lamins A and C | Quijana-roy 2008 | |
Autosomal dominant leukodystrophy | #169500 | Progressive neurological disorder characterized by symmetrical widespread myelin loss in the central nervous system | LMNB1, encoding lamin B1 | Padiath 2006 |
Barraquer-Simons syndrome, heterozygous mutations | #608709 | Acquired partial lipodystrophy | LMNB2, encoding lamin B2 | Hegele 2006 |
Dilated cardiomyopathy | #188380 | Increase in both left ventricular systolic and diastolic diameter and decrease in ejection fraction | LAP2a, encoding Lamin associated protein 2a | Taylor 2005 |
OMIM (Online Mendelian Inheritance in Man) is accessible at: http://www.ncbi.nlm.nih.gov/sites/entrez?db=OMIM