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Diversity in heritable disorders of connective tissue at a single center
Connective Tissue Research ( IF 2.9 ) Pub Date : 2020-09-08 , DOI: 10.1080/03008207.2020.1816994
Rai-Hseng Hsu, Yin-Hsiu Chien, Wuh-Liang Hwu, Ni-Chung Lee

ABSTRACT

Background

Heritable disorders of connective tissue (HDCT) is a heterogeneous group of conditions caused by defects in genes responsible for extracellular matrix elements. Although next-generation sequencing (NGS) technology can be used to analyze many genes at a time, precisely diagnosing HDCT is still challenging because of the overlapping phenotypes and genotypes.

Methods

A 67-gene NGS targeted panel or whole-exome sequencing was employed for the diagnosis of HDCT over 4 years. Phenotypes and genotypes of patients were analyzed retrospectively.

Results

Mutations in 16 genes were discovered in 34 patients with the suspicion of Ehlers-Danlos syndrome (n = 7), Marfan syndrome (n = 2), osteogenesis imperfecta (n = 3), skeletal dysplasia (n = 18), and others (n = 4). Eighteen patients were found to have mutations in collagen genes, three had SERPINF1 mutations, two had TRPV4 mutations, two had FBN1 mutations, two had COMP mutations, and mutations in seven other genes were found in one patient each. The eight patients with COL1A1 mutations had a wide variation in phenotype. Patients with COL3A1 and COL5A1 mutations presented with classic EDS, those with SERPINF1 mutations presented with typical OI type VI, those with TRPV4 mutations presented with severe spinal deformity, and those with COL2A1 mutations presented with syndromic or nonsyndromic bone dysplasia or only short stature.

Conclusion

A wide diversity in HDCT was observed. Therefore, knowledge about the phenotype-genotype correlation in HDCT is still crucial in the diagnosis of this group of diseases, and an improvement in the screening tool will be needed.



中文翻译:

单一中心结缔组织遗传性疾病的多样性

摘要

背景

遗传性结缔组织疾病 (HDCT) 是由负责细胞外基质元素的基因缺陷引起的一组异质性疾病。虽然下一代测序 (NGS) 技术可用于一次分析多个基因,但由于表型和基因型重叠,精确诊断 HDCT 仍然具有挑战性。

方法

67 基因 NGS 靶向 panel 或全外显子组测序用于诊断 HDCT 超过 4 年。回顾性分析患者的表型和基因型。

结果

在 34 名疑似 Ehlers-Danlos 综合征 (n = 7)、马凡综合征 (n = 2)、成骨不全症 (n = 3)、骨骼发育不良 (n = 18) 和其他患者中发现了 16 个基因的突变。 n = 4)。18 名患者发现胶原基因突变,3名 SERPINF1突变,2 名TRPV4突变,2 名FBN1突变,2 名COMP突变,另外 1 名患者中发现了其他 7 个基因的突变。8 名COL1A1突变患者的表型差异很大。具有COL3A1COL5A1突变的患者出现经典 EDS,具有SEPINF1的患者突变表现为典型的 OI 型 VI,具有TRPV4突变的表现为严重的脊柱畸形,而具有COL2A1突变的表现为综合征或非综合征性骨发育不良或仅身材矮小。

结论

观察到 HDCT 的广泛多样性。因此,了解 HDCT 中表型-基因型相关性对于诊断这组疾病仍然至关重要,需要改进筛查工具。

更新日期:2020-09-08
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