Gardner K, Barmada M M, Ptacek L J, Hoffman E P
Department of Neurology, University of Pittsburgh School of Medicine, PA 15213, USA.
Neurology. 1997 Nov;49(5):1231-8. doi: 10.1212/wnl.49.5.1231.
A single familial hemiplegic migraine locus has been previously mapped to 19p13.1 and associated with mutations in a calcium channel gene (CACNL1A4). We describe a new 39-member four-generation family from Wyoming of German-Native American descent with autosomal dominant familial hemiplegic migraine that is not linked to the chromosome 19p locus. Affected individuals showed a stereotypic pattern of migrainous headache associated with hemisensory and hemiparetic attacks, without other headache types. Eighty-three percent reported minor head trauma as a trigger for individual attacks. Seventy-two percent reported other typical migraine triggers for the attacks. Attack frequency decreased with age and the overall course was benign. Genetic linkage studies of this family found strong evidence for the disease gene in this family being located at chromosome 1q31. Multipoint analysis showed lod scores > 3 in a 44-cm region flanked by D1S158 and D1S2781, using 80% penetrance and a phenocopy rate of 1/50. Haplotype and multipoint analysis, including flanking markers, suggested incomplete penetrance and variable expressivity of the disease. A single affected patient who reports atypical symptoms including daily headaches likely represents a phenocopy. This new locus for hemiplegic migraine suggests that mutations of additional calcium channels in the region may cause the disease.
一个家族性偏瘫性偏头痛位点先前已被定位到19p13.1，并与一个钙通道基因（CACNL1A4）的突变相关。我们描述了一个来自怀俄明州的有39名成员的四代家族，其成员为德裔美国原住民后裔，患有常染色体显性家族性偏瘫性偏头痛，该疾病与19号染色体p位点不连锁。受影响个体表现出与偏身感觉和偏瘫发作相关的刻板偏头痛模式，无其他头痛类型。83%的人报告轻微头部外伤是单次发作的诱因。72%的人报告其他典型偏头痛诱因。发作频率随年龄降低，总体病程为良性。对该家族的基因连锁研究发现有力证据表明该家族的疾病基因位于1号染色体q31。多点分析显示，在以D1S158和D1S2781为侧翼的44厘米区域内，使用80%的外显率和1/50的拟表型率，连锁值>3。单倍型和多点分析，包括侧翼标记，提示该疾病存在不完全外显和可变表达。一名报告有非典型症状（包括每日头痛）的受影响患者可能代表一个拟表型。这个新的偏瘫性偏头痛位点表明该区域其他钙通道的突变可能导致该疾病。
