Identification of a Novel COL17A1 Compound Heterozygous Mutation in a Chinese Girl with Non-Herlitz Junctional Epidermolysis Bullosa
Identification of a Novel COL17A1 Compound Heterozygous Mutation in a Chinese Girl with Non-Herlitz Junctional Epidermolysis Bullosa
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中国女孩非赫利兹交界性大疱性表皮松解症中新型 COL17A1 复合杂合突变的鉴定
DOI：
10.1007/s11596-020-2234-9
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发表时间：
2020-08
影响因子：
2.4
通讯作者：
Zhou Min
中科院分区：
文献类型：
--
作者：
Yao Yan-yi;Zhang Yong;Xie Xiao-hui;Chen Lan;Zhu Feng;Zhou Min
非Herlitz交界性大疱性表皮松解症(JEB-NH)是一种常染色体隐性遗传性大疱性皮肤病，以出生后全身皮肤起水泡、牙齿畸形、全面性脱发和指甲营养不良为特征。潜在的缺陷是编码XVI型胶原的COL17A1基因突变，导致基底上皮细胞与基质附着的结构丢失。在目前的研究中，我们描述了一例先天性感染的10岁女孩，皮肤起水泡。皮肤科检查发现面部和手部有稀疏、轻微的水泡，牙齿有严重的釉质凹陷。先证者大疱性皮肤活检显示无棘层松解的真皮下大泡形成。抗XVI型胶原抗体染色的免疫荧光显示基底膜区XVI型胶原染色消失。结合全外显子测序和Sanger测序，发现COL17A1基因存在新的杂合性突变(c.4324C>；T；p.Q1442*和c.1834G>；C；p.G612R)，可能与所观察到的Jeb-NH相关。一个等位基因有一个新的无义突变(C.4324C>；T；p.Q1442*)，导致无义介导的mRNA衰退和XVII胶原蛋白的截短；另一个等位基因在外显子22有一个新的错义突变C.1834G>；C；p.G612R，导致Gly-X-Y三螺旋重复序列中甘氨酸到精氨酸的取代，降低了XVII胶原的热稳定性。我们的研究结果表明，基于WES的基因检测在诊断JEb-NH患者中是有用的。这些新发现的致病突变将进一步扩大我们对COL17A1基因与遗传性水疱病相关突变谱的理解。
Non-Herlitz junctional epidermolysis bullosa (JEB-nH), an autosomal recessive bullous genodermatosis, is characterized by generalized skin blistering from birth onward, dental anomalies, universal alopecia and nail dystrophy. The underlying defect is mutation of theCOL17A1gene encoding the type XVII collagen, resulting in losing structure for attachment of basal epithelial cells to the matrix. In present study, we described one case of congenitally affected female child aged 10 years, with skin blistering. Dermatologic examination revealed sparse, mild blisters on the face and hand, with profound enamel pitting of the teeth. Skin biopsy from proband’s bullous skin displayed subepidermal bulla formation without acantholysis. The immunofluorescence of anti-type XVII collagen antibody staining showed loss of type XVII collagen staining at the basement membrane zone. A combination of whole exome sequencing (WES) and Sanger sequencing revealed the novel heterozygous mutations (c.4324C>T;p.Q1442* and c.1834G>C;p.G612R) inCOL17A1gene, which could be associated with the observed JEB-nH. One allele had a novel nonsense mutation (c.4324C>T;p.Q1442*), resulting in nonsense-mediated mRNA decay and truncated collagen XVII; the other allele had a novel missense mutation of c.1834G>C;p.G612R in exon 22, causing a glycine-to-arginine substitution in the Gly-X-Y triple helical repeating motifs and decreasing the thermal stability of collagen XVII. Our findings indicate that the genetic test based on WES can be useful in diagnosing JEB-nH patients. The novel pathogenic mutations identified would further expand our understanding of the mutation spectrum ofCOL17A1gene in association with the inherited blistering diseases.
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DOI：
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发表时间：
2001
期刊：
The British journal of dermatology
影响因子：
--
作者：
G. Ashton;P. Sorelli;J. Mellerio;F. Keane;R. Eady;J. McGrath
通讯作者：
G. Ashton;P. Sorelli;J. Mellerio;F. Keane;R. Eady;J. McGrath
影响因子：
5.3
作者：
Meienberg J;Bruggmann R;Oexle K;Matyas G
通讯作者：
Matyas G
预测蛋白质突变的功能影响：在癌症基因组学中的应用。
影响因子：
14.9
作者：
Reva B;Antipin Y;Sander C
通讯作者：
Sander C
影响因子：
9.8
作者：
Li, Quan;Wang, Kai
通讯作者：
Wang, Kai
DOI：
--
发表时间：
2007
期刊：
--
影响因子：
--
作者：
通讯作者：
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