Panda Prateek Kumar, Sharawat Indar Kumar
Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand 249203, India.
Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand 249203, India.
Brain Dev. 2020 Apr;42(4):329-335. doi: 10.1016/j.braindev.2020.01.004. Epub 2020 Feb 6.
Still, the genetic basis of a large number of cases of early-onset isolated dystonia continues to be a mystery. In recent years, many new candidate genes are being identified as putative pathogenic factors in children with isolated dystonia due to the easy availability of whole-exome sequencing. Recently biallelic mutations in the COL6A3 gene were identified as a cause of rare dystonia (DYT)-27 syndrome. Till date, only six cases of DYT27 have been reported in the literature.
We report a new case of COL6A3 mutation associated early-onset isolated dystonia-DYT27. We did a review of the previously published cases of DYT27. Citations were identified through PubMed, Embase, Web of Science and Google scholar searches using the search terms (including variations), "Dystonia-27 or DYT27" or/and "COL6A3 mutation associated early-onset isolated dystonia", combined with study filters for original research, case reports and case series.
Next-generation sequencing in the index patient revealed two pathogenic compound heterozygous loss of function mutations in exon 10 and exon 12 of the COL6A3 gene coding for the alpha(α)3(VI) chain of type VI collagen. Together with the presented case, seven cases (five males) were available for analysis. The median age at onset was 22 years (range: 6-61). Dystonic symptoms were started from hands in five and from the neck in the remaining two patients. Five patients had favorable outcomes with trihexyphenidyl and botulinum toxin while tetrabenazine and levodopa were ineffective.
Although it is a new entity that is only recently discovered, in future years many more new cases suffering from this particular entity are likely to be reported and the already heterogeneous clinical spectrum is likely to be further widespread in years to come.
尽管如此，大量早发性孤立性肌张力障碍病例的遗传基础仍是个谜。近年来，由于全外显子测序易于获取，许多新的候选基因被确定为孤立性肌张力障碍儿童的潜在致病因素。最近，COL6A3基因的双等位基因突变被确定为罕见肌张力障碍（DYT）-27综合征的病因。迄今为止，文献中仅报道了6例DYT27病例。
我们报告了1例与COL6A3突变相关的早发性孤立性肌张力障碍-DYT27新病例。我们对先前发表的DYT27病例进行了回顾。通过PubMed、Embase、科学网和谷歌学术搜索，使用搜索词（包括变体）“肌张力障碍-27或DYT27”或/和“COL6A3突变相关的早发性孤立性肌张力障碍”，结合原始研究、病例报告和病例系列的研究筛选条件来确定文献引用。
索引患者的下一代测序显示，在编码VI型胶原α(α)3(VI)链的COL6A3基因第10外显子和第12外显子中存在两个致病性复合杂合功能丧失突变。连同本病例在内，共有7例（5例男性）可供分析。发病的中位年龄为22岁（范围：6 - 61岁）。5例患者的肌张力障碍症状始于手部，其余2例始于颈部。5例患者使用苯海索和肉毒杆菌毒素治疗效果良好，而丁苯那嗪和左旋多巴无效。
尽管这是一个最近才发现的新病种，但在未来几年可能会报告更多患这种特殊疾病的新病例，而且在未来几年，本已异质性的临床谱可能会进一步扩大。
