A mutation in SNAP29, coding for a SNARE protein involved in intracellular trafficking, causes a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma
A mutation in SNAP29, coding for a SNARE protein involved in intracellular trafficking, causes a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma
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DOI：
10.1086/432556
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发表时间：
2005-08-01
影响因子：
9.8
通讯作者：
Mandel, H
中科院分区：
文献类型：
--
作者：
Sprecher, E;Ishida-Yamamoto, A;Mandel, H
神经皮肤综合征代表了一个巨大的，很大程度上异质性的疾病组，其特征在于神经和皮肤病学的表现，反映了共同的胚胎起源的表皮和神经组织。在本报告中，我们描述了一种新的神经皮肤综合征的特点是脑发育不全，神经病变，鱼鳞病，角化病（CEDNIK综合征）。在两个大家族中使用纯合性作图，我们将疾病基因定位于22q11.2，并在所有患者中确定了SNAP 29中的1-bp缺失，该缺失编码参与囊泡融合的SNARE蛋白。SNAP 29的表达在患者的皮肤中降低，导致板层颗粒的异常成熟，并且因此导致表皮脂质和蛋白酶的错位。这些数据强调了囊泡运输调节机制对神经外胚层分化的重要性。
Neurocutaneous syndromes represent a vast, largely heterogeneous group of disorders characterized by neurological and dermatological manifestations, reflecting the common embryonic origin of epidermal and neural tissues. In the present report, we describe a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK syndrome). Using homozygosity mapping in two large families, we localized the disease gene to 22q11.2 and identified, in all patients, a 1-bp deletion in SNAP29, which codes for a SNARE protein involved in vesicle fusion. SNAP29 expression was decreased in the skin of the patients, resulting in abnormal maturation of lamellar granules and, as a consequence, in mislocation of epidermal lipids and proteases. These data underscore the importance of vesicle trafficking regulatory mechanisms for proper neuroectodermal differentiation.