Clinical and genetic heterogeneity in benign hereditary chorea
Clinical and genetic heterogeneity in benign hereditary chorea
复制标题
DOI：
10.1212/wnl.59.4.579
复制
发表时间：
2002-08-27
期刊：
影响因子：
9.9
通讯作者：
Arts, WFM
中科院分区：
文献类型：
--
作者：
Breedveld, GJ;Percy, AK;Arts, WFM
背景资料：良性遗传性舞蹈病（BHC）是一种常染色体显性遗传疾病，与亨廷顿舞蹈病的区别在于其起病早，病程稳定或仅轻微进展，且无智力减退。临床特征的变化是如此之大，以至于其存在受到怀疑。作者最近描述了一个荷兰大家庭中染色体14 q上负责BHC的基因的定位。目的：报告对这个荷兰家庭和其他六个BHC家庭进行广泛临床和连锁分析的结果。结果：7个家系中有3个与染色体14q13.1-q21.1连锁。HOMOG分析显示10 × 10（11）的优势有利于基因座异质性。连锁家庭的单倍型分析导致BHC基因的临界区间减少到8.4 cM之间的标记D14 S49和标记D14 S278。在临床上，这三个家庭有一个同质的图片与早发性舞蹈病，有时伴有轻微的共济失调，在步行，但没有肌张力障碍，肌阵挛抽搐，或构音障碍。在青春期或成年早期，舞蹈病运动的严重程度趋于减轻。在非连锁家族中，症状和体征在发病年龄和肌阵挛性抽搐或肌张力障碍的发生方面更为异质。结论：BHC是一种临床和遗传异质性疾病，一个明确的临床综合征定位于染色体14 q。
Background: Benign hereditary chorea (BHC) is an autosomal dominant disorder that can be distinguished from Huntington disease by its early onset, stable or only slightly progressive course, and absence of mental deterioration. The variation in clinical features is such that its very existence has been doubted. The authors recently described the localization of a gene responsible for BHC on chromosome 14q in a large Dutch family. Objective: To report results of extensive clinical and linkage analyses for this Dutch family and six other families with BHC. Results: Three of the seven families had linkage to a region on chromosome 14q13.1-q21.1. HOMOG analysis showed odds of 10 x 10(11) in favor of locus heterogeneity. Haplotype analyses for the linked families resulted in a reduction of the critical interval for the BHC gene to 8.4 cM between marker D14S49 and marker D14S278. Clinically, these three families had a homogeneous picture with early-onset chorea, sometimes accompanied by slight ataxia in walking, but without dystonia, myoclonic jerks, or dysarthria. The severity of the choreatic movements tended to abate in adolescence or early adulthood. In the unlinked families, symptoms and signs were more heterogeneous as to age at onset and the occurrence of myoclonic jerks or dystonia. Conclusions: BHC is a clinically and genetically heterogeneous disorder, with one well-defined clinical syndrome mapping to chromosome 14q.