Nedelea Florina, Veduta Alina, Duta Simona, Vayna Ana-Maria, Panaitescu Anca, Peltecu Gheorghe, Duba Hans-Christoph
Filantropia Clinical Hospital, Bucharest, Romania.
Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
J Med Life. 2018 Oct-Dec;11(4):343-345. doi: 10.25122/jml-2018-0076.
We present a family in which the first child was diagnosed with dopa-responsive dystonia based on biochemical findings only. Dopa-responsive dystonia is a severe heterogeneous genetic disease. The possibly involved genes are GCH1 and TH. In their second pregnancy, the parents came for genetic counseling and prenatal diagnosis late, at 12 weeks of gestation. Genetic testing in the affected child was performed, but the results were difficult to interpret. The identified mutations were classified as VOUS - variants of unknown clinical significance. Although possibly causative, a homozygous variant in the TH gene was not reported before in children with dopa-responsive dystonia. Due to limited time, establishing the fetal prognosis was challenging. Our report emphasizes the importance of a multidisciplinary approach in the context of new diagnostic techniques, such as Next Generation Sequencing. We illustrate the fact that behind any laboratory result remains sophisticated clinical judgment. We also describe a previously not reported variant of the TH gene in a child with severe, early-onset dystonia.
我们报告了一个家庭，其中的第一个孩子仅基于生化检查结果被诊断为多巴反应性肌张力障碍。多巴反应性肌张力障碍是一种严重的异质性遗传病。可能涉及的基因是GCH1和TH。在他们的第二次怀孕中，父母前来进行遗传咨询和产前诊断时已经很晚了，妊娠12周。对患病儿童进行了基因检测，但结果难以解释。所鉴定的突变被分类为意义未明的变异（VOUS）。尽管可能具有致病性，但TH基因中的纯合变异此前在多巴反应性肌张力障碍儿童中尚未有报道。由于时间有限，确定胎儿的预后具有挑战性。我们的报告强调了在新一代测序等新诊断技术背景下采用多学科方法的重要性。我们说明了任何实验室结果背后都需要复杂的临床判断这一事实。我们还描述了一名患有严重早发性肌张力障碍儿童中TH基因的一个此前未报道的变异。
