A Novel non-sense Mutation in Keratin 10 Causes a Familial Case of Recessive Epidermolytic Ichthyosis.
A Novel non-sense Mutation in Keratin 10 Causes a Familial Case of Recessive Epidermolytic Ichthyosis.
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DOI：
10.1002/mgg3.6
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发表时间：
2013-07-01
影响因子：
2
通讯作者：
Dunnwald, Martine
中科院分区：
文献类型：
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作者：
Gutierrez, Jeydith A;Hannoush, Zeina C;Vargas, Luis G;Momany, Allison;Garcia, Carmen C;Murray, Jeffrey C;Dunnwald, Martine
表皮松解性鱼鳞病(EI)是一种罕见的皮肤病，出生时以泛发性红皮病和皮肤起泡为特征，后来被角化过度所取代。它是由KRT1和KRT10高度保守区的常染色体显性突变引起的。到目前为止，只有4个常染色体隐性遗传的EI基因突变在血缘关系家族中被描述。它们都影响KRT10的2B结构域。在这项研究中，我们描述了4名EI患者(包括1例致命病例)，出生于委内瑞拉本土社区的一个近亲家庭，父母未受影响。这项研究的目的是描述该家族疾病的临床、遗传和形态方面的特征，并了解其功能含义。对KRT10和KRT1的基因组DNA进行测序。对皮肤活检标本进行角蛋白表达的免疫荧光检测。在皮肤活检组织学检查后，我们的结果显示角化过度，棘层松解，颗粒层扩大。KRT10的测序结果显示为无义突变(p.Tyr282Ter.)对应于患者的蛋白1B结构域和其他家庭成员的杂合型模式，导致完全缺乏K10。K10的缺失通过上调K14和K17的表达来补偿。总之，KRT10中的这个新突变是第一个不位于所谓的隐性EI“热点”的隐性遗传变异，这表明该基因的其他区域也容易发生这样的突变。
Epidermolytic ichthyosis (EI) is a rare skin disorder characterized by generalized erythroderma and cutaneous blistering at birth, which is substituted by hyperkeratosis later in life. It is caused by autosomal dominant mutations in highly conserved regions of KRT1 and KRT10. To date, only four mutations with autosomal recessive inheritance of EI have been described in consanguineous families. All of them affect the 2B domain of KRT10. In the present study, we describe four patients with EI (including one lethal case) born from unaffected parents in a consanguineous family of a native Venezuelan community. The objective of this study was to characterize the clinical, genetic, and morphological aspects of the disease in this family, as well as understand its functional implications. Genomic DNA was sequenced for KRT10 and KRT1. Immunofluoresence for keratin expression was performed on cutaneous biopsies. After examination of cutaneous biopsies histology, our results showed hyperkeratosis and acantholysis with an expanded granular layer. Sequencing of KRT10 demonstrated a nonsense mutation (p.Tyr282Ter.) corresponding to the 1B domain of the protein in patients and a heterozygous pattern in other family members, resulting in complete absence of K10. The loss of K10 was compensated by upregulation of K14 and K17. In conclusion, this novel mutation in KRT10 is the first recessive genetic variation that is not located in the so called “hot spot” for recessive EI, suggesting that other areas of the gene are also susceptible for such mutations.