Ferguson PJ, Chen S, Tayeh MK, Majeed HA, El-Shanti H. Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)

Baylor College of Medicine, Houston, Texas, United States
Journal of Medical Genetics (Impact Factor: 6.34). 08/2005; 42(7):551-7. DOI: 10.1136/jmg.2005.030759
Source: PubMed


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.
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.
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.
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.

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    • "None of the other genes within the microdeletion have been reported to be sensitive to hemizygosity. Homozygous mutations in lipin 2 (LPIN2) have been associated with Majeed syndrome, characterized by chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia [Ferguson et al., 2005]. METTL4 (methyltransferase-like 4) encodes for a putative methyltransferase of unknown function, whereas NDC80 encodes a central component of the kinetochore protein complex necessary for proper chromosome segregation and spindle checkpoint signaling [Martin- Lluesma et al., 2002]. "
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    • "Neutrophilic diseases share some clinical features with monogenic autoinflammatory disorders such as periodic fever and neutrophil infiltration in the skin and other organs. The SS was reported in monogenic disorders, such as Majeed syndrome [17]. But the differences in clinical manifestations, even within one group of ND, diversity in the subtypes of ND, and differences in the response to therapy [8] support the concept that neutrophilic diseases may be a new category named polygenic autoinflammatory diseases [1]. "
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