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Objective To investigate the clinical features,polysomnography,imaging examination,genetic analysis and laboratory examination of eight patients with familial fatal insomnia (FFI).Methods The clinical data,neuropsychological examination,results of cerebrospinal fluid analysis,imaging examination and polysomnography of eight patients with FFI in Xuanwu Hospital,Capital Medical University from 2009 to 2018 were retrospectively analyzed and summarized.Results Among the eight FFI patients,there were 3 males and 5 females,the onset age being (49.8+14.3) years (19 to 64 years) and the course of disease being eight to 18 months.D178N mutation in the PRNP gene of chromosome 20 and 129 amino acid polymorphisms of M/M were found in genetic examination in all the eight patients,of which five patients had family history.All the patients had sleep disorders,sleep-related involuntary movement,sleep-related dyspnea,laryngeal stridor.All the patients showed rapid progressive dementia with or without symptoms or signs of psychosis,ataxia,pyramidal and extrapyramidal.All the eight patients had progressive sympathetic symptoms,including hypertension,sweating,tachycardia,irregular breathing,and dysarthria.Cerebrospinal fluid 14-3-3 protein was found positive in one patient,and negative in seven patients.Electroencephalograph showed diffuse slow wave and non periodic synchronous discharge.Single-photon emission computed tomography or 18F fluorodeoxyglucose positron emission tomography showed decreased thalamic glucose metabolism in three patients.Seven patients showed decreased total sleep time,sleep awakening cycle disorder,especially the reduction or loss of rapid eye movement,laryngeal stridor and involuntary movement in polysomnography.Conclusions FFI is characterized by sleep disorder,sleep-related involuntary movement,dyspnea,laryngosis,rapid progressive dementia and sympathetic symptoms.The family history,polysomnography and positron emission tomography are helpful for the diagnosis of FFI.PRNP gene detection can confirm the diagnosis of FFI.
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ObjectiveTo investigate the relationship between the polymorphisms of the promoter of a disintegrin and metalloproteinase 10(ADAM10) gene and sporadic Alzheimer's disease (SAD).Methods The promoter of ADAM10 gene in 10 controls and 10 SAD patients was sequenced.Three variations were found,then these variations in 298 SAD patients (SAD group) and 315 healthy controls (control group)were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThree polymorphisms were found in the promoter of ADAM10 gene: -279G/A (rs653765),- 630G/T( rs514049 ) and - 921GAGA/- ( rs33926666 ).For - 921GAGA/-,there were significant differences in genotype ( GAGA/GAGA:138 (46.3％ ),GAGA/-:155(52.0％),-/-:5(1.7％))and allele frequencies (GAGA:431 (73.6％),-:165 (27.7％) ) between SAD and control (genotype:x2 =34.130,P =0.000; allele:x2 =25.972,P =0.000). For - 279G/A,there were significant differences in genotype and allele frequencies between SAD and control in the subjects without ApoEε4 allele (genotype:x2 =8.734,P=0.013; allele:x2 =5.129,P=0.024). -279G and -921GAGA were relatively protective allele types for SAD,and they were not in linkage disequilibrium.ConclusionThe polymorphisms - 279G/A and - 921GAGA/- of ADAM10 are associated with SAD.Allele G or genotype G/G of -279G/A and the GAGA/GAGA genotype or the GAGA allele of -921GAGA/- might have a protective effect on SAD.
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Objective To determine the risk factors and clinical features of mild vascular cognitive impairment due to subcortical small vessel disease (mVCI-SSVD).Methods Detailed demographic data,vascular risk factors, past and present history were collected and carefully neurological examination, National Institutes of Health Stroke Scale (NIHSS), as well as Hachinski ischemic score (HIS) were performed on 56 mVCI-SSVD patients.Further, the demographic data and vascular risk factors of mVCI-SSVD patients were compared with those of 80 normal control subjects.Results Proportions of smoking (39.3% (22/56)), hypertension (67.9% (38/56)), and diabetes (25.0% (14/56)) were higher in the patient group than in the normal control group (21.3% (17/80) , 47.5% (39/80), 11.3% (9/80)).Odds ratio (2.32(95% CI 1.05-5.13),2.15 (95% CI 1.02-4.54),2.26(95% CI 0.86-5.92)) between the two groups was statistically significant (P value: 0.039, 0.045, 0.047).There was no difference in terms of hyperlipidemia and cardiac disease between groups.Fifty percent (28/56) mVCI-SSVD patients had a clear stroke history.Twenty-six point eight percent (15/56) patients developed the cognitive impairment with an acute onset.Neurological focal signs presented in 20 patients (35.7%).Twenty four (42.9%) patients with HIS ≤ 4 points.Thirty eight cases (67.9%) scored 0 on NIHSS.Conclusions Current study suggested that smoking, hypertension, and diabetes may be risk factors for mVCI-SSVD.While hyperlipidemia and cardiac disease do not increase the risk of mVCI-SSVD.Unlike mVCI caused by large vessel disease, about half mVCI-SSVD patients lack of stroke history.Most patients show a relatively insidious onset and free of significant neurological focal signs.
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Objective To investigate the mechanisms of decreasing insulin degrading enzyme (IDE) level by mutation V97L in the gene presenilin 1 (PS-1).Methods Transcription factor GATA binding protein 3 (GATA-3) activity was assessed by protein/DNA array and verified by Western blot in SH-SY5Y cells transfected by PS-1 mutation V97L.Results Protein/DNA array and Western blot revealed that there was increased transcript factor activity (5.5 times high) and protein level of GATA-3 in V97L-PS-1 transfected SH-SY5Y cells.Transcription factor GATA-3 can bind to the IDE promoter and negatively control the IDE transcription level.Conclusion PS-1 mutation V97L may regulate the transcription of IDE via GATA-3, and subsequently involve in deposition of Aβ42 and development of Alzheimer's disease.