Null Leukemia Inhibitory Factor Receptor (LIFR) Mutations in Stüve-Wiedemann/Schwartz-Jampel Type 2 Syndrome

Nathalie Dagoneau, Deborah Scheffer, Céline Huber, Lihadh I. Al-Gazali, Maja Di Rocco, Anne Godard, Jelena Martinovic, Annick Raas-Rothschild, Sabine Sigaudy, Sheila Unger, Sophie Nicole, Bertrand Fontaine, Jean Luc Taupin, Jean François Moreau, Andrea Superti-Furga, Martine Le Merrer, Jacky Bonaventure, Arnold Munnich, Laurence Legeai-Mallet, Valérie Cormier-Daire

Research output: Contribution to journalArticlepeer-review

151 Citations (Scopus)


Stüve-Wiedemann syndrome (SWS) is a severe autosomal recessive condition characterized by bowing of the long bones, with cortical thickening, flared metaphyses with coarsened trabecular pattern, camptodactyly, respiratory distress, feeding difficulties, and hyperthermic episodes responsible for early lethality. Clinical overlap with Schwartz-Jampel type 2 syndrome (SJS2) has suggested that SWS and SJS2 could be allelic disorders. Through studying a series of 19 families with SWS/SJS2, we have mapped the disease gene to chromosome 5p13.1 at locus D5S418 (Zmax = 10.66 at θ = 0) and have identified null mutations in the leukemia inhibitory factor receptor (LIFR or gp190 chain) gene. A total of 14 distinct mutations were identified in the 19 families. An identical frameshift insertion (653_654insT) was identified in families from the United Arab Emirates, suggesting a founder effect in that region. It is interesting that 12/14 mutations predicted premature termination of translation. Functional studies indicated that these mutations alter the stability of LIFR messenger RNA transcripts, resulting in the absence of the LIFR protein and in the impairment of the JAK/STAT3 signaling pathway in patient cells. We conclude, therefore, that SWS and SJS2 represent a single clinically and genetically homogeneous condition due to null mutations in the LIFR gene on chromosome 5p13.

Original languageEnglish
Pages (from-to)298-305
Number of pages8
JournalAmerican Journal of Human Genetics
Issue number2
Publication statusPublished - Feb 2004

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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