A homozygous variant in the Lamin B receptor gene LBR results in a non-lethal skeletal dysplasia without Pelger-Huët anomaly

Meagan Collins, Valancy Miranda, Justine Rousseau, Lisa E. Kratz, Philippe M. Campeau

Research output: Contribution to journalArticlepeer-review

Abstract

Lamin B receptor, a member of the sterol reductase family, is an inner nuclear membrane protein which binds lamin B proteins and is involved in the organization of heterochromatin. Mutations in LBR have been associated with a variety of disorders, such as Pelger-Huët anomaly, a benign abnormality affecting neutrophils, and Greenberg Dysplasia, a lethal condition in the perinatal period. We identified a homozygous LBR missense mutation (NM_002296.4: c.1366C > G, p.(Leu456Val)) in two adult sisters with a Lamin B receptor-related disorder associated with a skeletal dysplasia milder than Greenberg Dysplasia. Individual 1 has short stature with short limbs (mostly rhizomelic for the upper extremities, and mesomelic for the lower extremities), limited elbow extension. She required Achilles tenotomy, and does not have facial dysmorphisms. Individual 2 has similar skeletal features, but also has bowed femurs, osteopenia, spastic paraplegia of the lower limbs, equinovarus feet, a single kidney, neurogenic bladder, obstructive hydronephrosis, scoliosis and syndactyly of the toes. This report provides additional evidence of variability for Lamin B receptor-related disorders associated with a non-lethal skeletal dysplasia without Pelger-Huët anomaly. We describe a novel pathogenic variant that has not been previously associated with disease and demonstrate the effect of this variant on sterol C14-reductase activity.

Original languageEnglish (US)
Article number115601
JournalBone
Volume141
DOIs
StatePublished - Dec 2020

Keywords

  • LBR
  • Lamin B receptor
  • Mesomelia
  • Rhizomelia
  • Skeletal dysplasia

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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