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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    ABSTRACT: The innate immune system is involved in the pathophysiology of systemic autoinflammatory diseases (SAIDs), an enlarging group of disorders caused by dysregulated production of proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α, in which autoreactive T-lymphocytes and autoantibodies are indeed absent. A widely deranged innate immunity leads to overactivity of proinflammatory cytokines and subsequent multisite inflammatory symptoms depicting various conditions, such as hereditary periodic fevers, granulomatous disorders, and pyogenic diseases, collectively described in this review. Further research should enhance our understanding of the genetics behind SAIDs, unearth triggers of inflammatory attacks, and result in improvement for their diagnosis and treatment.
    Mediators of Inflammation 07/2014; 2014:948154. DOI:10.1155/2014/948154 · 3.24 Impact Factor
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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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    ABSTRACT: Monogenic autoinflammatory syndromes (MAISs) are caused by innate immune system dysregulation leading to aberrant inflammasome activation and episodes of fever and involvement of skin, serous membranes, eyes, joints, gastrointestinal tract, and nervous system, predominantly with a childhood onset. To date, there are twelve known MAISs: familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, familial cold urticaria syndrome, Muckle-Wells syndrome, CINCA syndrome, mevalonate kinase deficiency, NLRP12-associated autoinflammatory disorder, Blau syndrome, early-onset sarcoidosis, PAPA syndrome, Majeed syndrome, and deficiency of the interleukin-1 receptor antagonist. Each of these conditions may manifest itself with more or less severe inflammatory symptoms of variable duration and frequency, associated with findings of increased inflammatory parameters in laboratory investigation. The purpose of this paper is to describe the main genetic, clinical, and therapeutic aspects of MAISs and their most recent classification with the ultimate goal of increasing awareness of autoinflammation among various internal medicine specialists.
    International Journal of Rheumatology 10/2013; 2013:513782. DOI:10.1155/2013/513782
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    • "NSAIDs can provide moderate improvement, and corticosteroids are useful in controlling chronic recurrent multifocal osteomyelitis and skin manifestations, but their long-term use in children is limited by metasteroidal comorbidities. In addition, long-term outcome with this strategy has been poor, with marked failure to thrive and permanent joint deformities [10, 142–145]. Recently, Herlin et al. reported a dramatic clinical, laboratory, and radiological improvement with either anakinra or canakinumab in 2 brothers with MS, opening up a new promising therapeutic avenue. "
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    ABSTRACT: Treatment of monogenic autoinflammatory disorders, an expanding group of hereditary diseases characterized by apparently unprovoked recurrent episodes of inflammation, without high-titre autoantibodies or antigen-specific T cells, has been revolutionized by the discovery that several of these conditions are caused by mutations in proteins involved in the mechanisms of innate immune response, including components of the inflammasome, cytokine receptors, receptor antagonists, and oversecretion of a network of proinflammatory molecules. Aim of this review is to synthesize the current experience and the most recent evidences about the therapeutic approach with biologic drugs in pediatric and adult patients with monogenic autoinflammatory disorders.
    Mediators of Inflammation 07/2013; 2013:939847. DOI:10.1155/2013/939847 · 3.24 Impact Factor
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