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Ultrastructural skin changes in Egyptian mandibuloacral dysplasia patients with p.Arg527Leu LMNA mutation and in their asymptomatic heterozygotic mothers
  1. Mohammad Al-Haggar1,
  2. Amany Shams2,
  3. Agnieszka Madej-Pilarczyk3,
  4. Tarik Barakat1,
  5. Monika Puzianowska-Kuznicka4,5
  1. 1 Genetics Unit, Pediatrics Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
  2. 2 Anatomy and Embryology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
  3. 3 Department of Neuromuscular Unit, Mossakowski Medical Research Centre, Warsaw, Poland
  4. 4 Department of Human Epigenetics, Mossakowski Medical Research Centre, Warsaw, Poland
  5. 5 Department of Geriatrics and Gerontology, Medical Center of Postgraduate Education, Warsaw, Poland
  1. Correspondence to Professor Mohammad Al-Haggar, Genetics Unit, Pediatrics Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; m.alhaggar{at}

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The LMNA gene encodes lamin A and lamin C, structural components of the nuclear lamina. 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. B-type lamins are permanently isoprenylated, whereas prelamin A loses its modification after incorporation into the lamina by lamin A-specific processing steps involving Zmpste24 endoprotease.4 ,5

The LMNA gene is located on chromosome 1q21.2–q21.3.6 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 …

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  • Correction notice This article has been corrected since it was published online first. An error in the title has been corrected, and the contributors statement has been updated.

  • Contributors MA was a principal investigator and contributed to study design, pedigree construction and writing of the manuscript; AS read and commented on the ultrastructural changes in biopsy specimens; AM correlated the data in protein analysis and electron microscopy; TB contributed to the review of literature and collection of samples; MP contributed to molecular diagnosis and revised the manuscript.

  • Funding The authors declare that they have not received any funds from any organising bodies in this work.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Mansoura University Children's Hospital Ethical Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.