Unit of Muscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, Rome, Italy.
Unit of Muscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, Rome, Italy.
Eur J Paediatr Neurol. 2017 Nov;21(6):873-883. doi: 10.1016/j.ejpn.2017.07.009. Epub 2017 Jul 22.
Collagen VI-related disorders (COL6-RD) are a group of heterogenous muscular diseases due to mutations in the COL6A1, COL6A2 and COL6A3 genes, encoding for collagen VI, a critical component of the extracellular matrix. Ullrich congenital muscle disorder and Bethlem myopathy represent the ends of a clinical spectrum that includes intermediate phenotypes of variable severity. UCMD are caused by recessive loss of function mutations or de-novo dominant-negative mutations. The intermediate phenotype and BM are more commonly caused by dominantly acting mutations, and less commonly by recessive mutations. Recently parental mosaicism for dominant mutations in COL6 have been reported in four COL6-RD families and germinal mosaicism has been also identified in a family with recurrence of UCMD in two half-sibs.
Here we report three unrelated patients affected by a COL6-RD who carried de novo mosaic mutations in COL6A genes. These mutations, missed by Sanger sequencing, were identified by next generation sequencing.
This report highlights the importance of a complete diagnostic workup when clinical and histological finding are consistent with a COL6-RD and strengthen the impression that mosaicisms are underestimated events underlying COL6-RD.
胶原 VI 相关疾病（COL6-RD）是一组异质性肌肉疾病，由 COL6A1、COL6A2 和 COL6A3 基因突变引起，这些基因编码胶原 VI，这是细胞外基质的关键组成部分。先天性肌营养不良症和 Bethlem 肌病代表了一个临床谱的两端，其中包括不同严重程度的中间表型。UCMD 是由隐性功能丧失突变或新生显性负性突变引起的。中间表型和 BM 更常见于显性作用突变引起，而较少由隐性突变引起。最近，在四个 COL6-RD 家族中报道了 COL6 中显性突变的父母镶嵌现象，并且在一个 UCMD 在两个半同胞中复发的家族中也鉴定出了生殖细胞镶嵌现象。
在这里，我们报告了三个无关的 COL6-RD 患者，他们携带 COL6A 基因的新生镶嵌突变。这些突变通过桑格测序漏检，通过下一代测序鉴定。
本报告强调了在临床和组织学表现与 COL6-RD 一致的情况下进行全面诊断的重要性，并进一步证实了镶嵌现象是 COL6-RD 被低估的潜在机制。
