Novel clinical features and pleiotropic effect in three unrelated patients with LMNA variant

Clin Dysmorphol. 2021 Jan;30(1):10-16. doi: 10.1097/MCD.0000000000000355.


LMNA gene encodes A-type lamins and the encoded proteins join the structure of the nuclear lamina and affect the processes of nuclear homeostasis, DNA replication, repair, transcription, and apoptosis. LMNA variants cause a heterogeneous group of diseases known as laminopathies. Phenotypes associated with LMNA variants mainly affect the heart, skeleton, skin, bones, and nervous system. The affected tissues may vary depending on the site of the variant on the gene and the variation type. Complex phenotypes may also occur in some cases, in which findings of premature aging, cardiomyopathy, mandibuloacral dysplasia, lipodystrophy, renal involvement, metabolic involvement, and myopathy coexist. The pleiotropic effect of LMNA variants can result in heterogeneous phenotypes. In this study, we aimed to describe atypical phenotypic characteristics in a patient with familial partial lipodystrophy type 2 associated with LMNA variant, another with mandibuloacral dysplasia, and a third patient with a complex phenotype as well as discuss them in the context of their relationship with the genotype.

Publication types

  • Case Reports

MeSH terms

  • Alleles
  • Biological Variation, Population
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genotype
  • Humans
  • Lamin Type A / genetics*
  • Laminopathies / diagnosis*
  • Laminopathies / genetics*
  • Lipodystrophy, Congenital Generalized / diagnosis
  • Lipodystrophy, Congenital Generalized / genetics
  • Organ Specificity
  • Phenotype*


  • LMNA protein, human
  • Lamin Type A