摘要
目的观察血管型Ehlers-Danlos综合征(vEDS,OMIM#130050)先证者伴随听力损失的新表型,并对小鼠耳蜗中COL3A1蛋白定位表达进行动态观察。方法收集伴听力损失的vEDS先证者散发家系的患者资料,并运用全外显子组测序技术对患者遗传学病因进行鉴定;通过免疫荧光技术对COL3A1蛋白在小鼠耳蜗组织血管纹结构中的时序性定位表达进行了分析;利用单细胞测序数据库对COL3A1在血管纹特定细胞中的表达模式进行探讨。结果先证者存在浅表皮肤瘀伤、身材矮小、下颌短缩及拇指挛缩畸形等改变,并呈现为混合型听力损失表型。遗传学病因鉴定结果显示患者携带COL3A1基因致病性突变c.3775G>A(p.A1259T)。免疫荧光结果显示,7日龄小鼠耳蜗血管纹结构中COL3A1蛋白表达缺失,在1月龄小鼠血管纹结构中该蛋白表达显著,然而在6月龄和12月龄逐渐下降。单细胞测序结果显示COL3A1在血管纹中特异性表达在血管周围巨噬细胞样黑色素细胞上,其表达水平随着年龄的增长而下降。结论本研究丰富了COL3A1基因突变所致vEDS的听力损失新表型。小鼠耳蜗中COL3A1蛋白定位于血管纹并存在时序性表达差异,为后续探索COL3A1相关性听力损失的机制提供实验依据。
Objective To report a novel hearing loss phenotype in a patient with vascular Ehlers-Danlos syndrome(vEDS,OMIM#130050)and to investigate the dynamic localization and expression of COL3A1 protein in the mouse cochlea.Methods We collected clinical data from a sporadic family case of vEDS with hearing loss to identify genetic etiology using whole-exome sequencing technology.Immunofluorescence staining was employed to examine the temporal localization of COL3A1 protein in the vascular stria of mouse cochlear tissue.Furthermore,we explored the expression patterns of COL3A1 in specific cells of the vascular stria using single-cell sequencing databases.Results The proband exhibited superficial skin bruising,short stature,mandibular hypoplasia,and thumb contractures,along with a mixed hearing loss phenotype.Genetic analysis revealed a de novo pathogenic mutation in the COL3A1 gene(c.3775G>A).Immunofluorescence results showed weak COL3A1 protein expression in the stria vascularis in 7-day-old mice,significant expression in 1-month-old mice,and a gradual decline in 6-and 12-month-old mice.Single-cell sequencing indicated that COL3A1 was specifically expressed in perivascular macrophage-like melanocytes in the stria vascularis,with expression levels decreasing with age.Conclusions This study enriches the understanding of the novel hearing loss phenotype associated with COL3A1 mutations in vEDS.The temporal and spatial expression of COL3A1 in the stria vascularis of the mouse cochlea provides experimental evidence supporting further exploration into the mechanisms underlying COL3A1-related hearing loss.
作者
王璐
陈岸海
徐震航
吴学文
WANG Lu;CHEN Anhai;XU Zhenhang;WU Xuewen(Department of Otolaryngology-Head and Neck Surgery,Xiangya Hospital,Central South University,Otolaryngology Major Disease Research Key Laboratory of Hunan Province,National Clinical Research Center for Geriatric Disorders(Xiangya Hospital),Changsha 410008,China)
出处
《中华耳科学杂志》
2026年第5期401-405,共5页
Chinese Journal of Otology
基金
国家自然科学基金项目(82371169)
湖南省自然科学基金项目(2021JJ31108)。
