Journal article
Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)
Journal of medical genetics, Vol.42(7), pp.551-557
07/2005
DOI: 10.1136/jmg.2005.030759
PMCID: PMC1736104
PMID: 15994876
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.
Details
- Title: Subtitle
- Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)
- Creators
- P Ferguson - Department of Pediatrics, Division of Hematology/Oncology/Rheumatology, University of Iowa, Iowa City, IA, USAS Chen - Department of Pediatrics, Division of Hematology/Oncology/Rheumatology, University of Iowa, Iowa City, IA, USAM Tayeh - Department of Pediatrics, Division of Hematology/Oncology/Rheumatology, University of Iowa, Iowa City, IA, USAL Ochoa - Department of Pediatrics, Division of Hematology/Oncology/Rheumatology, University of Iowa, Iowa City, IA, USAS Leal - Department of Pediatrics, Division of Hematology/Oncology/Rheumatology, University of Iowa, Iowa City, IA, USAA Pelet - Department of Pediatrics, Division of Hematology/Oncology/Rheumatology, University of Iowa, Iowa City, IA, USAA Munnich - Department of Pediatrics, Division of Hematology/Oncology/Rheumatology, University of Iowa, Iowa City, IA, USAS Lyonnet - Department of Pediatrics, Division of Hematology/Oncology/Rheumatology, University of Iowa, Iowa City, IA, USAH Majeed - Department of Pediatrics, Division of Hematology/Oncology/Rheumatology, University of Iowa, Iowa City, IA, USAH El-Shanti - Department of Pediatrics, Division of Hematology/Oncology/Rheumatology, University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Journal of medical genetics, Vol.42(7), pp.551-557
- DOI
- 10.1136/jmg.2005.030759
- PMID
- 15994876
- PMCID
- PMC1736104
- NLM abbreviation
- J Med Genet
- ISSN
- 0022-2593
- eISSN
- 1468-6244
- Publisher
- BMJ Group
- Language
- English
- Date published
- 07/2005
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Rheumatology, Allergy, and Immunology
- Record Identifier
- 9984070760202771
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