A Novel LMNA Mutation Causes Altered Nuclear Morphology and Symptoms of Familial Partial Lipodystrophy (Dunnigan

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B Saha1, D Lessel, F M Hisama

  • 1Department of Pathology, University of Washington, Seattle, Wash., USA.

Molecular Syndromology
|October 30, 2010
PubMed

Insights

Familial partial lipodystrophy type 2 (FPLD2), caused by LMNA mutations, should be considered in Werner syndrome diagnoses. A novel LMNA mutation, P485R, was identified in a patient with progeroid features.

Area of Science:

  • Genetics
  • Molecular Biology
  • Endocrinology

Background:

  • Dunnigan-type partial lipodystrophy (FPLD2) is a genetic disorder often caused by mutations in the LMNA gene.
  • Progeroid syndromes, like Werner syndrome, share some clinical features with lipodystrophies, complicating diagnosis.

Purpose of the Study:

  • To investigate a potential novel genetic cause of FPLD2 in a patient presenting with Werner syndrome-like features.
  • To analyze the pathogenicity of a newly identified LMNA mutation.

Main Methods:

  • Genetic sequencing to identify mutations in the LMNA and WRN genes.
  • Immunocytochemical analysis of primary fibroblast and lymphoblastoid cell lines to assess nuclear morphology.

Main Results:

  • A novel heterozygous LMNA mutation, P485R, was identified in a patient with progeroid features who was wild type for the WRN gene.
  • The mutation is located near canonical FPLD2 mutations in exon 8 of LMNA.
  • Abnormal nuclear morphology, indicative of laminopathy, was observed in patient-derived fibroblasts but not in lymphoblastoid cells.

Conclusions:

  • The novel LMNA mutation P485R is associated with Dunnigan-type partial lipodystrophy (FPLD2).
  • FPLD2 should be included in the differential diagnosis for patients presenting with features of Werner syndrome.
  • Cell-type-specific effects of laminopathies may influence diagnostic findings.

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