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J Med Genet 42:551-557 doi:10.1136/jmg.2005.030759
  • Original article

Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)

  1. P J Ferguson1,
  2. S Chen2,
  3. M K Tayeh3,
  4. L Ochoa4,
  5. S M Leal5,
  6. A Pelet6,
  7. A Munnich7,
  8. S Lyonnet8,
  9. H A Majeed9,
  10. H El-Shanti10
  1. 1Department of Pediatrics, Division of Hematology/Oncology/Rheumatology, University of Iowa, Iowa City, IA, USA
  2. 2Department of Pediatrics, University of Iowa, Iowa City, IA, USA
  3. 3Department of Pediatrics, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA, USA
  4. 4Department of Pediatrics, University of Iowa, Iowa City, IA, USA
  5. 5Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
  6. 6Department of Medical Genetics, INSERM U393, Hôpital Necker-Enfants Malades, Paris, France
  7. 7Department of Medical Genetics, INSERM U393, Hôpital Necker-Enfants Malades, Paris, France
  8. 8Department of Medical Genetics, INSERM U393, Hôpital Necker-Enfants Malades, Paris, France
  9. 9Department of Pediatrics, University of Jordan, Amman, Jordan
  10. 10Department of Pediatrics, Division of Medical Genetics, University of Iowa, Iowa City, IA, USA
  1. Correspondence to:
 Hatem El-Shanti
 University of Iowa Hospital, 2615 JCP, 200 Hawkins Drive, Iowa City, IA 52242, USA; hatem-el-shantiuiowa.edu
  • Received 5 January 2005
  • Accepted 18 February 2005
  • Revised 16 February 2005

Abstract

Background: Majeed syndrome is an autosomal recessive, autoinflammatory disorder characterised by chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia. The objectives of this study were to map, identify, and characterise the Majeed syndrome causal gene and to speculate on its function and role in skin and bone inflammation.

Methods: Six individuals with Majeed syndrome from two unrelated families were identified for this study. Homozygosity mapping and parametric linkage analysis were employed for the localisation of the gene responsible for Majeed syndrome. Direct sequencing was utilised for the identification of mutations within the genes contained in the region of linkage. Expression studies and in silico characterisation of the identified causal gene and its protein were carried out.

Results: The phenotype of Majeed syndrome includes inflammation of the bone and skin, recurrent fevers, and dyserythropoietic anaemia. The clinical picture of the six affected individuals is briefly reviewed. The gene was mapped to a 5.5 cM interval (1.8 Mb) on chromosome 18p. Examination of genes in this interval led to the identification of homozygous mutations in LPIN2 in affected individuals from the two families. LPIN2 was found to be expressed in almost all tissues. The function of LPIN2 and its role in inflammation remains unknown.

Conclusions: We conclude that homozygous mutations in LPIN2 result in Majeed syndrome. Understanding the aberrant immune response in this condition will shed light on the aetiology of other inflammatory disorders of multifactorial aetiology including isolated chronic recurrent multifocal osteomyelitis, Sweet syndrome, and psoriasis.

Footnotes

  • H El-Shanti was supported by “Chaire Internationale de Recherche, Blaise Pascal, de l’etat et de la Règion d’Ile-de-France” which is managed with further support by the “Fondation de l’Ecole Normale Supèrieure” when the project started (1999–2000). P Ferguson receives funding from the NIH/NICHD Children’s Health Research Center Grant, the University of Iowa’s Department of Pediatrics, and the Roy J. and Lucille A. Carver College of Medicine.

  • Competing interests: none declared