Ultrastructural skin changes in Egyptian mandibuloacral dysplasia patients with p.Arg527Leu LMNA mutation and in their asymptomatic heterozygotic mothers

The nuclear lamina of nuclear envelope (NE) is a scaffold, which provides structural and mechanical stability for the NE; it consists primarily of type V intermediate filament proteins (A-type and B-type lamins) and many inner nuclear membrane proteins. 1 2 Interaction of lamins with heterochromatin and with transcriptional regulators suggests the importance of their role in the maintenance of chromatin organisation and ingene expression. 3 At the NE periphery, lamin precursors undergo a series of post-translational modifications. 6 Its coding region spans approximately 24 kb and contains 12 exons; alternative splicing within exon 10 gives rise to two different mRNAs that code for prelamin A and lamin C. 7 Different diseases have been ascribed to mutations in this gene including these affecting skin, cardiac and/or skeletal muscles, nerves, fat tissue and bones. 8 One of the diseases associated with the LMNA mutations is Hutchinson-Gilford progeria syndrome (HGPS), usually arising due to the de novo heterozygous single base change (GGC>GGT) in exon 11 creating an abnormal splice donor site and resulting in the production of truncated protein, progerin. 9-12 HGPS is a very rare, fatal disorder characterised by postnatal growth retardation, midface hypoplasia, premature atherosclerosis, absence of subcutaneous fat, alopecia and generalised osteodysplasia with osteolysis and pathological fractures. 9 10 13 The skin of children with HGPS has atrophic epidermis, dermal fibrosis (scleroderma-like with thickening, disorganisation and hyalinisation of collagen bundles), thin or absent hypodermis and a complete loss of skin appendages or decrease in number of sebaceous glands and hair follicles.