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LBR mutation and nuclear envelope defects in a patient affected with Reynolds syndrome
  1. Caroline Gaudy-Marqueste1,2,
  2. Patrice Roll2,3,
  3. Vera Esteves-Vieira3,
  4. Pierre-Jean Weiller4,
  5. Jean Jacques Grob1,
  6. Pierre Cau2,3,
  7. Nicolas Lévy2,3,
  8. Annachiara De Sandre-Giovannoli2,3
  1. 1Service de Dermatologie, Hôpital Ste Marguerite, Marseille, France
  2. 2Inserm UMR_S910, Faculté de Médecine la Timone, Marseille, France
  3. 3Département de Génétique Médicale et Biologie Cellulaire, Hôpital d'Enfants La Timone, Marseille, France
  4. 4Service de Médecine Interne, Hôpital La Timone, Université Aix-Marseille II, Marseille, France
  1. Correspondence to Dr Annachiara De Sandre-Giovannoli, Laboratoire de Génétique Moléculaire, Département de Génétique Médicale, Hôpital d'Enfants la Timone, 264 Rue St. Pierre, Marseille 13385, France; annachiara.desandre{at}


Background Lamins are proteins of the nuclear envelope involved in ‘laminopathies’, an heterogeneous group of diseases sharing clinical similarities with systemic sclerosis (SSc).

Methods In this context, a search was undertaken for mutations in LMNA, encoding Lamins A/C, and ZMPSTE24, LBR, LMNB1, LMNB2, MAN1, SYNE1a and LAP2, encoding Lamins A/C molecular partners, in a Caucasian woman affected with Reynolds syndrome, a particular nosologic entity specifically associating limited cutaneous SSc and primary biliary cirrhosis.

Results Coding regions and intron-exon boundaries of these genes were PCR amplified and sequenced, revealing a single heterozygous missense mutation in LBR exon 9 (c.1114C/T; p.R372C). This variant was absent in 400 control chromosomes. The mutation was predicted to induce a change in Lamin B receptor (LBR) tertiary structure and molecular interactions by bioinformatic tools. Further functional explorations were performed on the patient's fibroblasts and lymphoblastoid cell lines. On the latter, the expression levels of LBR, Lamins A/C, Lamin B1, Lamin B2, and HP1a were conserved. Conversely, in the patient's skin fibroblasts, LBR and the aforementioned molecular partners showed dramatically reduced or abolished expression levels. The immunofluorescence analyses performed on both cell lines corroborated these findings.

Conclusion The fibroblast specific abnormalities observed suggest that this particular LBR mutation might have dominant negative deleterious effects in a tissue specific fashion, possibly through the perturbation of the interactions or stability of the nuclear envelope protein network. LBR mutations might thus be associated with Reynolds syndrome.

  • Laminopathies
  • systemic sclerosis
  • lamin B receptor
  • nuclear envelope
  • primary biliary cirrhosis
  • Reynolds syndrome
  • dermatology
  • genetics

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  • Competing interests None.

  • Patient consent Obtained.

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