RIN2 Deficiency Results in Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis: MACS Syndrome
RIN2 Deficiency Results in Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis: MACS Syndrome
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DOI：
10.1016/j.ajhg.2009.07.001
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发表时间：
2009-08-14
影响因子：
9.8
通讯作者：
Sprecher, Eli
中科院分区：
文献类型：
--
作者：
Basel-Vanagaite, Lina;Sarig, Ofer;Sprecher, Eli
遗传性弹性组织疾病代表了一组复杂而异质的疾病，其特征通常是皮肤下垂，偶尔会出现危及生命的内脏并发症。在本研究中，我们报告了一种常染色体隐性遗传疾病，我们称之为MACS综合征（大头畸形，脱发，皮肤拉克萨和脊柱侧凸）。该疾病被定位于染色体20 p11.21-p11.23，并且在RIN 2中发现了纯合移码突变，该突变在一个大型血缘亲属中与疾病表型分离。鉴定的突变导致RIN 2表达降低，RIN 2是一种普遍表达的蛋白质，与Rab 5相互作用并参与内吞运输的调节。发现RIN 2缺乏与真皮微纤维缺乏和fibulin-5缺乏相关，这可能是患者显示的异常皮肤表型的基础。
Inherited disorders of elastic tissue represent a complex and heterogeneous group of diseases, characterized often by sagging skin and occasionally by life-threatening visceral complications. In the present study, we report on an autosomal-recessive disorder that we have termed MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis). The disorder was mapped to chromosome 20p11.21-p11.23, and a homozygous frameshift mutation in RIN2 was found to segregate with the disease phenotype in a large consanguineous kindred. The mutation identified results in decreased expression of RIN2, a ubiquitously expressed protein that interacts with Rab5 and is involved in the regulation of endocytic trafficking. RIN2 deficiency was found to be associated with paucity of dermal microfibrils and deficiency of fibulin-5, which may underlie the abnormal skin phenotype displayed by the patients.