A splice site mutation confirms the role of LPIN2 in Majeed syndrome

Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States
Arthritis & Rheumatology (Impact Factor: 7.76). 03/2007; 56(3):960-4. DOI: 10.1002/art.22431
Source: PubMed


Majeed syndrome is an autoinflammatory disorder consisting of chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and neutrophilic dermatosis. To date, 2 unrelated families with Majeed syndrome have been reported. Mutations in LPIN2 have been found in both families. Here we report a third consanguineous family with Majeed syndrome with a novel mutation. The patient, a 3-year-old Arabic girl, had hepatosplenomegaly and anemia as a neonate. At age 15 months, she developed recurrent episodes of fever and multifocal osteomyelitis. In addition, bone marrow aspiration demonstrated significant dyserythropoiesis, suggesting Majeed syndrome. Coding sequences and splice sites of LPIN2 were sequenced in the patient and her mother. A homozygous single-basepair change was detected in the donor splice site of exon 17 (c.2327+1G>C) in the patient; her mother was heterozygous at this site. These data confirm the role of LPIN2 mutations in the etiology of Majeed syndrome.

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    • "Majeed syndrome is a rare autosomal recessive clinical entity, first identified in 1989, caused by mutations in the LPIN2 gene, localized on the short arm of chromosome 18, which codifies the lipin-2 protein, expressed in liver, kidney, gastrointestinal tract, lymphatic tissue, and bone marrow [126]. Lipin-2 regulates proinflammatory signals determined by saturated fatty acids, and its mutated variant leads to chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and neutrophilic dermatosis, usually around the second year of life [127, 128]. Skin lesions start with erythematosus papules and well-defined painful plaques all over the body, often resembling Sweet's syndrome or psoriasis. "
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    • "Clinically, this syndrome is characterized by recurrent fever attacks associated with multifocal sterile osteomyelitis, dyserythropoietic anemia, and chronic diffuse neutrophilic dermatosis with onset in early childhood [142]. Its treatment is empirically based on the use of NSAIDs and corticosteroids, although excellent results have recently been described with administration of anakinra and canakinumab [144, 145]. "
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