Laminopathy encompasses a broad range of rare genetic disorders brought about by a mutation in the human genetic structure. The part of the gene affected is responsible for encoding proteins of the nuclear lamina.
The primary building blocks of the nuclear lamina are nuclear intermediate filament proteins called lamin. Among other functions, lamins are responsible for providing shape and mechanical stability to the nuclear lamina.
Laminopathy is caused by mutations in human lamins, which lead to many different heritable diseases that affect various tissues, and can also cause early aging. Cells taken from such patients of laminopathy can be seen to have an abnormal nuclear shape and structure. This, in turn, affects both the mechanical properties and the function of the nucleus.
Other than this nuclear deformation, there are also believed to be other effects of this mutation – especially on the lamin filament assembly – but these are as yet unknown.
The overall impaired nuclear mechanics, and the increased fragility of the nuclear envelope, are believed to be at least partly culpable for the muscular phenotypes that are found in many laminopathies, such as limb-girdle muscular dystrophy and Emery-Dreifuss muscular dystrophy.
The mutation also causes the cells to exhibit an increased sensitivity to mechanical strain and fluid shear stress. This plays a role in atherioslcerosis – a thickening of the artery wall – that is the leading cause of death among patients of the Hutchinson-Gilford progeria syndrome.
Laminopathies fall into two major categories: primary laminopathies and secondary laminopathies.
Primary laminopathies are caused by a mutation in the lamin A/C (LMNA) gene and fall into five classes. Each class affects a specific tissue in an isolated fashion, which includes striated muscles, peripheral nerves, adipose tissue, or a systematic effect on several tissues – as in the event of premature aging syndromes and their related disorders – that is known as “systematic laminopathy.”
The fifth class pertains to clinical reports of certain forms of heterogeneous situations where the disorder is characterized by a coexistence of two or more affected tissues. In this case, the disorder comprises of an overlapping phenotype as a result of this coexistence.
Secondary laminopathies, on the other hand, are caused by a mutation in the FACE-1 gene. These affect the normal posttranslational processing of prelamin A.
Overall, there is much research that still needs to be done in order to fully understand the effects of different laminopathies, as the relations between phenotypes and genotypes are far from clear at the current moment. Various treatments are provided to help cope with the many effects of laminopathy on the human body, although there is no cure for the disorder itself.
