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.