Mutations in TITF-1 are associated with benign hereditary chorea
Mutations in TITF-1 are associated with benign hereditary chorea
复制标题
DOI：
10.1093/hmg/11.8.971
复制
发表时间：
2002-04-15
影响因子：
3.5
通讯作者：
Heutink, P
中科院分区：
文献类型：
--
作者：
Breedveld, GJ;van Dongen, JWF;Heutink, P
良性遗传性舞蹈病(MIM 118700)是一种常染色体显性遗传性运动障碍。症状的早期出现(通常在5岁之前)，以及观察到在一些BHC家庭中，症状在成年后趋于减少，表明这种疾病是大脑发育障碍的结果。与亨廷顿病(MIM 143100)不同，BHC是非进行性的，患者的智力正常或略低于正常。有相当大的家庭间和家庭内的变异性，包括构音障碍、轴性肌张力障碍和步态障碍。之前，我们在14号染色体上确定了一个六六六基因座，随后又发现了与同一基因座连锁的其他独立家系。对所有14号染色体连锁家系的重组分析最初导致BHC基因在标记D14S49和D14S278之间的临界间隔减少到8.4 cM。对一个小型BHC家族的关键区域进行了更详细的分析，发现含有TITF-1基因的1.2Mb从头缺失，TITF-1基因是一种含有同源结构域的转录因子，对肺、甲状腺和基底神经节的器官发生至关重要。在这里，我们报告了TITF-1突变与BHC相关的证据。
Benign hereditary chorea (BHC) (MIM 118700) is an autosomal dominant movement disorder. The early onset of symptoms (usually before the age of 5 years) and the observation that in some BHC families the symptoms tend to decrease in adulthood suggests that the disorder results from a developmental disturbance of the brain. In contrast to Huntington disease (MIM 143100), BHC is non-progressive and patients have normal or slightly below normal intelligence. There is considerable inter- and intrafamilial variability, including dysarthria, axial dystonia and gait disturbances. Previously, we identified a locus for BHC on chromosome 14 and subsequently identified additional independent families linked to the same locus. Recombination analysis of all chromosome 14-linked families resulted initially in a reduction of the critical interval for the BHC gene to 8.4 cM between markers D14S49 and D14S278. More detailed analysis of the critical region in a small BHC family revealed a de novo deletion of 1.2 Mb harboring the TITF-1 gene, a homeodomain-containing transcription factor essential for the organogenesis of the lung, thyroid and the basal ganglia. Here we report evidence that mutations in TITF-1 are associated with BHC.