Study On The Relationship Between Familial Migraine's Differentiation Of Symptoms And Signs For Classification Of Syndrome And Gene CACNA1A

Background: Migraine is a common type of primary headache, which manifests itself as attacks of often severe, throbbing head pain with nausea, vomiting and sensory sensitivity to light and sound. Its etiology is still unclear. However it's usually thought to be associated with genitics and envierenment. Familial hemiplegic migraine is a rare autosomal dominant migraine with aura. FHM mutations so far identified include those in CACNA1A, ATPIA2 and SCNIA genes. Among them, CACNA1A gene was best investigated. So far, fifteen different missense mutations have been identified in the CACNAlA gene, related to 11 different exons. But the association of CACNA1A gene and conmon types of migraine is still unclear. There are many versions about the pathogenesis in tradictional Chinese midicine (TCM). Generally speaking, it concerns with wind, cold, fire, phlegm, deficiency and stagnant blood. But until now, there isn't an analysis specialized in the etiology of familial migraine and it's differentiation of symptoms and signs for classification of syndrome.Objective: To investigate the fundation of invasion in TCM in familial migraine, and its etiology of molecular genetics.Methods: There were two groups in the part of clinical observation, the observative group contained 20 migraineurs with family history, the control group contained 25 migraineurs without family history. We differentiated symptoms and signs for classification of syndrome according to the patients' clinical manifestation, and analyzed the different features between distributions in the pattern of syndrome with statistical methods. Scoring all patients with a renal deficiency factors scale to identify whether the differences of the relationship between the attacks of migraine and renal deficiency between the two groups were obvious in statistics. In the empirical study part, we detected 11 exons of CACNA1A gene in 20 familial migraineurs and 15 health adults through DNA abstraction, PCR-SSCP and DNA sequencing to investigate the association of CACNA1A gene and familial migraine.Results: In the comparison of patients' general state of migraine, it indicated that the age of onset in observative group is younger (23.85±9.41, 28.68±8.00, P=0.07), and the course of disease is longer (8.15±6.77, 4.05±3.98, P=0.015). Familial migraineurs' deficiency of kidney-essence was maximum in the pattern of syndrome, but the syndrome of blood stasis in cerebral collaterals predominated in the migraineurs without family history. There was an obvious statistical significance between two groups in distribution of patterns of syndrome (P=0.020). Scores of renal deficiency factors scale were obviously higher in migraineures with family history than those without family history (20.60±4.86,16.96±3.07, P=0.004). In empirical study part, we found 3 different abnormal migrative bands in exons 16, 25 and 27 in three patients through PCR-SSCP. After DNA sequencing, we only identified G2094A mutation in exert 16 in patient 11, which is an synonymous mutation, without changing the encoding of amino acids. We found the same synonymous mutation in the patient' s doughter with DNA sequencing. We didn't found any abnormal migrative band in 15 heath adults in the control group.Conclusion: Deficiency of kidney-essence is a common etiological factor in the attack of familial migraine. It's also probably the foundation of invasion of familial migraine. The G2094A found with DNA sequencing is the first mutation that is identified in migraine in China. The mutation is a synonymous mutation, without changing the encoding of amino acids, which are both threomine before and after mutation. In conventional idea, synonymous mutation didn't impact the expression of protein, so it won't lead to diseases. But recent research indicate that synonymous mutation or SNP may impact the expression of protein through some steps of many component elements, like transcription, translation after transcription, posttranslational processing and et al. Therefore, G2094A mutation may lead to migraine through above-mentioned pathway, and the mutation of CACNA1A gene is possiblly related to the attack of miagrain. The pattern of syndrome of two migraineurs with mutation are both deficiency of kidney-essence, which suggest that migraineurs with deficiency of kidney-essence maybe more liabilitive to mutate. Because of the small sample size and the low mutation rate, the conclusion of our study needs to be confirmed in large sample in China.