Study Of Association Between Mutation Of Tau 3' UTR,5' UTR,Intron 9 And Sporadic Amyotrophic Lateral Sclerosis

Objective:To analyze the clinical features in cases of sporadic amyotrophic lateral sclerosis(SALS), investigate the association between mutation of Tau 3′UTR,5′UTR,intron 9 and SALS, provide evidence for early diagnosis.Methods:The clinical dates and peripheral venous blood of 66 cases of confirmed SALS,41 cases of unconfirmed SALS,40 of controls was collected. We statistical analyzed the clinical records of SALS, and the tau 3′UTR,5′UTR,intron 9 was evaluated by DNA sequence analysis in subjects with SALS and controls, in order to find mutation points, investigate the association between the mutations and SALS.Results: 40 cases (24 definite, 1 probable, 7 possible, 8 suspected) had complete clinical records. The mean age at oneset was 52.4±12.5 years, onset before 30 years old and 75 years old was less. Male to female ratio was 5:3. It attacked more in manual workers than in brain workers, but this conclusion was uncertain, maybe it was relevant with the constituent ratio of patients. An insidious onset and slowly deterioration is very common, the hypodynamia of the upper extremities was the most common initial symptom, then develops from the initial location to the near motor neuron vertically or horizontally, finally with glossopharyngeal paralysis and quadriplegia. The cause of the 3 dead was pulmonary infection. EMG was abnormal and shows neurogenic damage in all the 36 subjects examined. 34 were taken sternocleidomastoid muscles electromyography, the positive rate was 58.8%. 2 were taken electromyography of paraspinal muscles, the results was positive. A few shew aged encephalatrophy or spine degeneration by imaging examination. The target gene of all the patients and controls was amplified and sequenced. We found 20 tau mutation points, 9 in the 3′UTR, 1 in the 5′UTR, 10 in the intron 9. By chi-square statistics, only the frequencies of 105788A→G significantly differed between patients and controls (P=0.031), confirmed SALS and controls(P=0.008), confirmed and unconfirmed (P=0.034).Conclusions:SALS mainly onset when middle-aged, males were significantly more than females, and it follows invariably developing regularity. EMG and MRI has important value in the diagnosis and differential diagnosis of ALS. The diagnosis of ALS is mainly depend on clinical sign yet. By DNA sequence analysis, we found 20 mutation points, among which the mutation of 105788A→G was significantly happened more common in the confirmed SALS. We guess this mutation increase the risk for ALS, for it locates in intron 9, and causing ALS by chang the 4R to 3R subtype ratio.