Fernandez Desiree M, Hand Collette K, Sweeney Brian J, Parfrey Nollaig A
Department of Neurology, Cork University Hospital, Wilton, Cork, Ireland.
Headache. 2008 Jan;48(1):101-8. doi: 10.1111/j.1526-4610.2007.00848.x.
We studied a large Irish Caucasian pedigree with familial hemiplegic migraine (FHM) with the aim of finding the causative gene mutation.
FHM is a rare autosomal-dominant subtype of migraine with aura, which is linked to 4 loci on chromosomes 19p13, 1q23, 2q24, and 1q31. The mutations responsible for hemiplegic migraine have been described in the CACNA1A gene (chromosome 19p13), ATP1A2 gene (chromosome 1q23), and SCN1A gene (chromosome 2q24).
We performed linkage analyses in this family for chromosome 1q23 and performed mutation analysis of the ATP1A2 gene.
Linkage to the FHM2 locus on chromosome 1 was demonstrated. Mutation screening of the ATP1A2 gene revealed a G to C substitution in exon 22 resulting in a novel protein variant, D999H, which co-segregates with FHM within this pedigree and is absent in 50 unaffected individuals. This residue is also highly conserved across species.
We propose that D999H is a novel FHM ATP1A2 mutation.
我们研究了一个患有家族性偏瘫性偏头痛（FHM）的大型爱尔兰白种人家系，旨在寻找致病基因突变。
FHM是偏头痛伴先兆的一种罕见的常染色体显性亚型，与19p13、1q23、2q24和1q31染色体上的4个基因座相关。已在CACNA1A基因（19p13染色体）、ATP1A2基因（1q23染色体）和SCN1A基因（2q24染色体）中描述了导致偏瘫性偏头痛的突变。
我们对这个家系的1q23染色体进行了连锁分析，并对ATP1A2基因进行了突变分析。
证实与1号染色体上的FHM2基因座连锁。ATP1A2基因的突变筛查显示，外显子22发生了G到C的替换，产生了一种新的蛋白质变体D999H，它在这个家系中与FHM共分离，在50名未受影响的个体中不存在。这个残基在物种间也高度保守。
我们提出D999H是一种新的FHM ATP1A2突变。
