Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)
Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)
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DOI：
10.1136/jmg.2005.030759
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发表时间：
2005-07-01
影响因子：
4
通讯作者：
El-Shanti, H
中科院分区：
文献类型：
--
作者：
Ferguson, PJ;Chen, S;El-Shanti, H
背景：马吉德综合征是一种常染色体隐性自身炎症性疾病，其特征为慢性复发性多灶性骨髓炎和先天性红细胞生成不良性贫血。本研究的目的是定位、识别和描述马吉德综合征的致病基因，并推测其在皮肤和骨骼炎症中的功能和作用。
方法：本研究确定了来自两个无亲缘关系家庭的6名马吉德综合征患者。采用纯合性定位和参数连锁分析来定位马吉德综合征的致病基因。利用直接测序来识别连锁区域内基因的突变。对所识别的致病基因及其蛋白质进行了表达研究和计算机模拟特性分析。
结果：马吉德综合征的表型包括骨骼和皮肤炎症、反复发热以及红细胞生成不良性贫血。简要回顾了6名患者的临床表现。该基因被定位到18号染色体短臂上一个5.5厘摩（1.8兆碱基对）的区间。对该区间基因的检测导致在两个家庭的患者中发现了LPIN2基因的纯合突变。发现LPIN2在几乎所有组织中都有表达。LPIN2的功能及其在炎症中的作用仍然未知。
结论：我们得出结论，LPIN2基因的纯合突变导致马吉德综合征。了解这种情况下的异常免疫反应将有助于阐明其他多因素病因的炎症性疾病的病因，包括孤立性慢性复发性多灶性骨髓炎、斯威特综合征和银屑病。
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.