Markova E D, Slominskiĭ P A, Illarioshkin S N, Miklina N I, Shadrina M I, Popova S N, Limborskaia S A, Ivanova-Smolenskaia I A
Institute of Neurology, Russian Academy of Medical Sciences, Moscow, Russia.
Genetika. 2000 Jul;36(7):952-8.
For the first time in Russia, analysis of the GCH-I and DYT1 genes was carried out for the purpose of direct DNA diagnostics in families with various forms of hereditary torsion dystonia (TD). Four new missense mutations (Met102Lys, Thr94Lys, Cys141Trp, and Ser176Thr) in the GCH-I gene were found in patients with dopa-responsive dystonia (DRD), testifying to a genetic heterogeneity of this clinical form of TD. The distribution of the major del GAG mutation in exon 5 of the DYT1 gene was studied in patients with non-dopa-responsive dystonia (NDRD). In total, the mutation was found in 68% of the patients. The frequency of this mutation in Ashkenazi Jews with NDRD was 100% (twice higher than in Slavonic families), suggesting the founder effect reported for NDRD in this ethnic group. Mutations of the GCH-I and DYT1 genes were also found in patients with atypical and questionable cases of TD, which are difficult to diagnose with methods other than DNA analysis. The data obtained made it possible to extend the spectrum of clinical signs of DRD and NDRD and to revise the views on true penetrance of the corresponding mutant genes, which is important for medical genetic counseling in affected families.
在俄罗斯首次对各种形式的遗传性扭转性肌张力障碍（TD）家庭进行了GCH - I和DYT1基因分析，以进行直接DNA诊断。在多巴反应性肌张力障碍（DRD）患者中发现了GCH - I基因的四个新错义突变（Met102Lys、Thr94Lys、Cys141Trp和Ser176Thr），这证明了这种临床形式的TD存在遗传异质性。对非多巴反应性肌张力障碍（NDRD）患者研究了DYT1基因第5外显子主要的del GAG突变分布。总共在68%的患者中发现了该突变。在患有NDRD的德系犹太人中，该突变频率为100%（比斯拉夫家庭高两倍），表明在这个种族群体中存在NDRD所报道的奠基者效应。在非典型和疑难TD病例患者中也发现了GCH - I和DYT1基因的突变，这些病例用DNA分析以外的方法难以诊断。所获得的数据使得能够扩展DRD和NDRD的临床体征谱，并修正对相应突变基因真实外显率的看法，这对于受影响家庭的医学遗传咨询很重要。
