Valente E M, Bentivoglio A R, Cassetta E, Dixon P H, Davis M B, Ferraris A, Ialongo T, Frontali M, Wood N W, Albanese A
Department of Clinical Neurology, Institute of Neurology, London, United Kingdom.
Ann Neurol. 2001 Mar;49(3):362-6.
Primary torsion dystonia (PTD) is a clinically and genetically heterogeneous group of movement disorders, usually inherited in an autosomal dominant fashion with reduced penetrance. The DYT1 gene on chromosome 9q34 is responsible for most cases of early limb-onset PTD. Two other PTD loci have been mapped to date. The DYT6 locus on chromosome 8 is associated with a mixed phenotype, whereas the DYT7 locus on chromosome 18p is associated with adult onset focal cervical dystonia Several families have been described in which linkage to the known PTD loci have been excluded. We identified a large Italian PTD family with 11 definitely affected members. Phenotype was characterized by prominent cranial-cervical and upper limb involvement and mild severity. A genome-wide search was performed in the family. Linkage analysis and haplotype construction allowed us to identify a novel PTD locus (DYT13) within a 22 cM interval on the short arm of chromosome 1, with a maximum lod score of 3.44 between the disease and marker D1S2667.
原发性扭转性肌张力障碍（PTD）是一组临床和遗传异质性的运动障碍疾病，通常以常染色体显性方式遗传，外显率降低。位于9号染色体长臂34区的DYT1基因是大多数早发性肢体型PTD病例的致病基因。迄今已确定了另外两个PTD基因座。位于8号染色体的DYT6基因座与混合型表型相关，而位于18号染色体短臂的DYT7基因座与成人发病的局限性颈部肌张力障碍相关。已有多个家系被报道，其中与已知PTD基因座的连锁关系已被排除。我们鉴定了一个大型意大利PTD家系，其中有11名确诊患者。其表型特征为显著的颅颈和上肢受累，且症状较轻。我们对该家系进行了全基因组搜索。连锁分析和单倍型构建使我们在1号染色体短臂上一个22厘摩区间内确定了一个新的PTD基因座（DYT13），疾病与标记物D1S2667之间的最大对数优势得分为3.44。
