Clinical and pathophysiological delineation of musculocontractural Ehlers-Danlos syndrome caused by dermatan sulfate epimerase deficiency (mcEDS-DSE): A detailed and comprehensive glycobiological and pathological investigation in a novel patient.

IF 3.3 2区医学 Q2 GENETICS & HEREDITY

Human Mutation Pub Date : 2022-12-01 DOI:10.1002/humu.24437

Mari Minatogawa, Takuya Hirose, Shuji Mizumoto, Tomomi Yamaguchi, Chiai Nagae, Masashi Taki, Shuhei Yamada, Takafumi Watanabe, Tomoki Kosho

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引用次数: 4

Abstract

Musculocontractural Ehlers-Danlos syndrome caused by dermatan sulfate epimerase deficiency (mcEDS-DSE) is a rare connective tissue disorder. This is the first report describing the detailed and comprehensive clinical and pathophysiological features of mcEDS-DSE. The patient, with a novel homozygous nonsense variant (NM_013352.4:c.2601C>A:p.(Tyr867*)), exhibited mild skin hyperextensibility without fragility and small joint hypermobility, but developed recurrent large subcutaneous hematomas. Dermatan sulfate (DS) moieties on chondroitin sulfate/DS proteoglycans were significantly decreased, but remained present, in skin fibroblasts. Electron microscopy examination of skin specimens, including cupromeronic blue-staining to visualize glycosaminoglycan (GAG) chains, revealed coexistence of normally assembled collagen fibrils with attached curved GAG chains and dispersed collagen fibrils with linear GAG chains from attached collagen fibrils across interfibrillar spaces to adjacent fibrils. Residual activity of DS-epi1, encoded by DSE, and/or compensation by DS-epi2, a minor homolog of DS-epi1, may contribute to the mild skin involvement through this "mosaic" pattern of collagen fibril assembly.

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由皮肤硫酸酯epimase缺乏症(mcEDS-DSE)引起的肌肉收缩性ehers - danlos综合征的临床和病理生理描述:对一位新患者进行了详细而全面的糖生物学和病理研究。

由皮肤硫酸酯epimase缺乏症(mcEDS-DSE)引起的肌肉收缩性ehers - danlos综合征是一种罕见的结缔组织疾病。这是第一篇详细而全面地描述mcEDS-DSE临床和病理生理特征的报道。该患者为一种新型纯合无义变异(NM_013352.4:c.2601C> a:p.(Tyr867*))，表现为轻度皮肤过伸性，无脆性，关节轻度过度活动，但复发性大皮下血肿。在皮肤成纤维细胞中，硫酸软骨素/硫酸软骨素蛋白聚糖上的硫酸皮肤蛋白(DS)部分显著降低，但仍存在。皮肤标本的电子显微镜检查，包括铜丙烯蓝染色以显示糖胺聚糖(GAG)链，显示正常组装的胶原原纤维与附着的弯曲GAG链共存，分散的胶原原纤维与线性GAG链共存，从附着的胶原原纤维穿过纤维间间隙到邻近的原纤维。由DSE编码的DS-epi1的残余活性和/或DS-epi2 (DS-epi1的次要同源物)的补偿，可能通过胶原纤维组装的“马赛克”模式导致轻度皮肤受累。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Mutation 医学-遗传学

CiteScore

8.40

自引率

5.10%

发文量

190

审稿时长

2 months

期刊介绍： Human Mutation is a peer-reviewed journal that offers publication of original Research Articles, Methods, Mutation Updates, Reviews, Database Articles, Rapid Communications, and Letters on broad aspects of mutation research in humans. Reports of novel DNA variations and their phenotypic consequences, reports of SNPs demonstrated as valuable for genomic analysis, descriptions of new molecular detection methods, and novel approaches to clinical diagnosis are welcomed. Novel reports of gene organization at the genomic level, reported in the context of mutation investigation, may be considered. The journal provides a unique forum for the exchange of ideas, methods, and applications of interest to molecular, human, and medical geneticists in academic, industrial, and clinical research settings worldwide.