Nuclear Lamin Disease

Mutations in lmna cause autosomal dominant severe heart disease accounting for 10 of dilated cardiomyopathy dcm.

Nuclear lamin disease. New findings on lamin functions in various cellular processes and emphasizes the relationship between the lamins and devastating diseases ranging. J biol chem 1993 268 16321 6. Nuclear lamins interact with inner nuclear membrane proteins to form the nuclear lamina on the interior of the nuclear envelope. Structural organization of the human gene encoding nuclear lamin a and nuclear lamin c.

The nuclear lamina consists of two components lamins and nuclear lamin associated membrane proteins. Lamin a c haploinsufficiency causes dilated cardiomyopathy and apoptosis triggered cardiac conduction system disease. As more and more unrelated diseases were linked to lamins and other nuclear envelope proteins nuclear structure and disease became an increasingly prominent research focus. Disease causing mutations in the human lmnb1 and lmnb2 genes are extremely rare.

When mutations in nuclear lamins were first identified in skeletal and cardiac muscle diseases the molecular events underlying pathogenesis were mere points of speculation. Some of these are located in the α helical central rod domain required for the polymerization of the nuclear lamins into higher order structures. We used wounded nih 3t3 fibroblast monolayers to explore whether disease associated lamin a variants affected nuclear or centrosome positioning events that orient the centrosome toward the wound edge in this system the serum factor lysophosphatidic acid lpa activates cdc42 dependent pathways that trigger actin and myosin ii dependent rearward nuclear movement away from the. Numerous mutations in the human a type lamin gene lmna cause the premature aging disease progeria.

Lamins a and c are intermediate filament nuclear envelope proteins encoded by the lmna gene. Nuclear lamin functions and disease. Patient cells with a mutation in this domain 433g a e145k show severely lobulated nuclei a separation of the a and b type lamins. Wolf cm wang l alcalai r et al.

Gentzon hall md phd in chronic kidney disease dialysis and transplantation fourth edition 2019. Characterised by progressive conduction system disease arrhythmia and systolic impairment lamin a c heart disease is more malignant than other common dcms due to high event rates even. Lin f worman hj. The most extensively studied of these adult onset autosomal dominant leukodystrophy adld is caused by duplication of lmnb1 the pathology of this disease includes slow degeneration of myelin in the central nervous system followed by pyramidal signs ataxia and impaired.

Lamins have elastic and mechanosensitive properties and can alter gene regulation in a feedback response to mechanical cues. The nuclear lamina is a dense fibrillar network of structural proteins that lines the inner nuclear membrane of eukaryotic cells. The lamins are type v intermediate filaments which can be categorized as either a type lamin a c or b type lamin b 1 b 2 according to homology of their dna sequences biochemical properties and cellular localization during the cell cycle.