Epidermal barrier abnormalities in exfoliative ichthyosis with a novel homozygous loss-of-function mutation in CSTA
Epidermal barrier abnormalities in exfoliative ichthyosis with a novel homozygous loss-of-function mutation in CSTA
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DOI：
10.1111/bjd.13545
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发表时间：
2015-06-01
影响因子：
10.3
通讯作者：
Gruber, R.
中科院分区：
文献类型：
--
作者：
Moosbrugger-Martinz, V.;Jalili, A.;Gruber, R.
常染色体隐性剥脱性鱼鳞病（AREI）是由编码半胱氨酸蛋白酶抑制剂A（胱抑素A）的CSTA突变引起的。我们提出了一个25岁的男子从伊朗与近亲的父母，谁提出了先天性红皮病，多汗症和弥漫性角化过度粗糙掌跖皮肤脱皮，加重暴露于水和闭塞。候选基因分析揭示了一个以前未知的纯合功能丧失突变c。172 C> T（p.Arg58Ter），免疫组化显示表皮cystatin A缺失，证实了AREI的诊断。透射电子显微镜超微结构分析显示正常降解的角化桥粒，轻度细胞间水肿的棘层，但不是在基底层，正常出现桥粒，和突出的角蛋白丝内的基底角质形成细胞。皮质包膜厚度减少，板层脂质双层被打乱，板层体分泌过早发生，分泌的板层体内容物的处理被延迟。这些屏障异常使人联想到（尽管不如内瑟顿内瑟顿综合征严重）由丝氨酸蛋白酶抑制剂LEKTI缺乏引起的内瑟顿综合征。这项工作描述了超微结构的研究结果与表皮屏障异常的证据在AREI。
Autosomal recessive exfoliative ichthyosis (AREI) results from mutations in CSTA, encoding cysteine protease inhibitor A (cystatin A). We present a 25-year-old man from Iran with consanguineous parents, who presented with congenital erythroderma, hyperhidrosis and diffuse hyperkeratosis with coarse palmoplantar peeling of the skin, aggravated by exposure to water and by occlusion. Candidate gene analysis revealed a previously unknown homozygous loss-of-function mutation c. 172C> T (p.Arg58Ter) in CSTA, and immunostaining showed absence of epidermal cystatin A, confirming the diagnosis of AREI. Ultrastructural analysis by transmission electron microscopy showed normal degradation of corneodesmosomes, mild intercellular oedema in the spinous layer but not in the basal layer, normal-appearing desmosomes, and prominent keratin filaments within basal keratinocytes. Thickness of cornified envelopes was reduced, lamellar lipid bilayers were disturbed, lamellar body secretion occurred prematurely and processing of secreted lamellar body contents was delayed. These barrier abnormalities were reminiscent of (albeit less severe than in) Netherton syndrome, which results from a deficiency of the serine protease inhibitor LEKTI. This work describes ultrastructural findings with evidence of epidermal barrier abnormalities in AREI.