Ophoff R A, Terwindt G M, Vergouwe M N, van Eijk R, Mohrenweiser H, Litt M, Hofker M H, Haan J, Ferrari M D, Frants R R
MGC Department of Human Genetics, Leiden University, The Netherlands.
Eur J Hum Genet. 1996;4(6):321-8.
Familial hemiplegic migraine (FHM) is an autosomal domianant subtype of migraine with attacks, associated with transient episodes of hemiparesis. One of the genes for FHM has been assigned to chromosome 19p13. Detailed analysis of critical recombinants from two different chromosome 19-linked FHM families, using new markers indicated a 6-cM candidate region on 19p13.1-p13.2 flanked by loci D19S394 and D19S226. Another paroxysmal neurological disorder, episodic ataxia type 2 (EA-2), has also been linked to the same chromosomal region. Most of the interval was completely covered by YAC and cosmid contigs; the physical map yielded approximately 3 Mb encompassing several genes including the protein kinase substrate 80K-H (PRKCSH) gene. Since PRKCSH is involved in neuronal signal transduction, it was considered to be an FHM candidate gene. The genomic structure of this gene was established and mutation analysis for all exon and flanking intron sequences was performed in FHM- and EA-2-affected individuals. Five polymorphisms were identified, including a trinucleotide repeat length variation in the coding sequence. However, no potential disease causing mutation was found and therefore the PRKCSH gene can be excluded for both FHM and EA-2.
家族性偏瘫性偏头痛（FHM）是偏头痛的一种常染色体显性亚型，发作时伴有偏瘫的短暂发作。FHM的一个基因已被定位于19号染色体短臂1区3带（19p13）。利用新的标记对来自两个不同的与19号染色体连锁的FHM家系的关键重组体进行详细分析，结果表明在19p13.1 - p13.2上有一个6厘摩（cM）的候选区域，两侧是基因座D19S394和D19S226。另一种发作性神经系统疾病，2型发作性共济失调（EA - 2），也与同一染色体区域相关。该区间的大部分被酵母人工染色体（YAC）和黏粒重叠群完全覆盖；物理图谱产生了大约3兆碱基（Mb），包含几个基因，包括蛋白激酶底物80K - H（PRKCSH）基因。由于PRKCSH参与神经元信号转导，它被认为是FHM的候选基因。确定了该基因的基因组结构，并对FHM和EA - 2患者的所有外显子和侧翼内含子序列进行了突变分析。鉴定出五个多态性，包括编码序列中的三核苷酸重复长度变异。然而，未发现潜在的致病突变，因此PRKCSH基因可被排除与FHM和EA - 2相关。
