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

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.

Autoinflammatory diseases and the inflammasome: mechanisms of IL-1β activation leading to neutrophil-rich skin disorders

“…Majeed syndrome has only been reported in Jordan and is caused by mutations in LPIN2 [28][29] . This rare disease is defined by an association of CRMO with congenital dyserythropoietic anemia and neutrophilic dermatosis, although the role of lipin 2 in bone and skin-localized inflammation remains unknown.…”

Síndromes autoinflamatórias hereditárias na faixa etária pediátrica

“…122 It is caused by mutations in the LPIN2 gene, which codes for an eponymous protein. 123 Thus far, only nine associated mutations have been described. 18 Patients with Majeed syndrome present with early (mostly neonatal) onset of chronic recurrent multifocal osteomyelitis, neutrophilic dermatitis, and congenital dyserythropoietic anemia.…”

“…122,125 Bone biopsy reveals nonspecific granulocytic infiltration. 123,125 Antibiotics are of no use in the treatment of Majeed syndrome. 7,125 Some patients may benefit from therapy with NSAIDs, corticosteroids, interferon gamma, bisphosphonates, and anti-TNF agents.…”

Osteolytic Lesion in PAPA Syndrome Responding to Anti-interleukin 1 Treatment

“…The Journal of on April 6, 2019 -Published by www.jrheum.org Downloaded from receptor antagonist) syndromes, and the multifactorial CRMO 6,7,8 . A good response to IL-1 blockers has been reported in all these conditions 7,8,9 .…”