ABSTRACT
OBJECTIVE@#To report a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifesting as lumbago, hunchback and Parkinson's syndrome.@*METHODS@#A 49-years-old male CADASIL patient was reported. Results of clinical examination, neuroimaging and genetic testing were analyzed. His family members were also subjected to genetic testing. Related literature was reviewed.@*RESULTS@#The patient had no typical symptoms of CADASIL such as headache, repeated stroke, dementia and emotional disorders, but progressive Parkinson's syndrome, late onset lumbago, hunchback, dysphagia, and diplopia. Brain MRI showed left basal ganglia and external capsule lacunar infarction. Genetic testing revealed a point mutation c.1630C>T (p.R544C) in exon 11 of the NOTCH3 gene. A heterozygous mutation was detected in the same gene in his mother, elder sister and younger brother, all of whom showed different clinical phenotypes.@*CONCLUSION@#The clinical features of CADASIL are heterogeneous. Lumbago, humpback, and Parkinson's syndrome may be a rare clinical phenotype of CADASIL.
Subject(s)
Humans , Male , Middle Aged , CADASIL , Genetics , Low Back Pain , Magnetic Resonance Imaging , Mutation , Parkinson Disease , Receptor, Notch3 , GeneticsABSTRACT
Objective@#To report a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifesting as lumbago, hunchback and Parkinson’s syndrome.@*Methods@#A 49-years-old male CADASIL patient was reported. Results of clinical examination, neuroimaging and genetic testing were analyzed. His family members were also subjected to genetic testing. Related literature was reviewed.@*Results@#The patient had no typical symptoms of CADASIL such as headache, repeated stroke, dementia and emotional disorders, but progressive Parkinson’s syndrome, late onset lumbago, hunchback, dysphagia, and diplopia. Brain MRI showed left basal ganglia and external capsule lacunar infarction. Genetic testing revealed a point mutation c. 1630C>T (p.R544C) in exon 11 of the NOTCH3 gene. A heterozygous mutation was detected in the same gene in his mother, elder sister and younger brother, all of whom showed different clinical phenotypes.@*Conclusion@#The clinical features of CADASIL are heterogeneous. Lumbago, humpback, and Parkinson’s syndrome may be a rare clinical phenotype of CADASIL.
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Objective To study the neuroprotective role of TFP5 in a MPTP-induced mouse model of Parkinson's disease (PD).Methods C57BL/6 mice were used as experimental animals.Briefly, 5 consecutive days of intraperitoneal injection of 25 mg/Kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was applied to induce mouse PD model.The mice were randomized into 5 groups including control group,model group, scrambled TFP5 peptide (Scb) group, TFP5 group and roscovitine group.On the 7th day after the first injection of MPTP,behavior tests were performed, and then western blot method was employed to detect the expression of p25 and phosphorylated MEF2D in substantia nigra.Tyrosine hydroxylase (TH) immunohistochemical staining was performed to observe the apoptosis of dopaminergic neurons in substantia nigra pars compacta (SNpc) 28 days after the first injection of MPTP.Results MPTP increased the expression of p25 (0.48±0.10 vs 0.26±0.02, P＜0.05) and phosphorylated MEF2D (0.81±0.10 vs 0.22±0.02, P＜0.05) in substantia nigra, but decreased the number of dopaminergic neurons in SNpc (348.67±24.40 vs 463.29± 19.61, P＜0.05),resulting in motor impairment in the model mice (P＜0.05).Intraperitoneal injection of 30mg/Kg of TFP5 for 3 days effectively reduced the excessive phosphorylation of MEF2D (0.25 ± 0.12 vs 0.81 ± 0.10, P＜ 0.05) in substantia nigra, rescued dopaminergic neuron reduction of SNpc (422.92±8.41 vs 348.67±24.40, P＜0.05), and improved the motor ability of the model mice (P ＜0.05).Roscovitine exerted almost same neuroprotective role as TFP5 ,while Scb had no protective effect.Conclusion TFP5 can rescue MPTP-induced damage of dopaminergic neurons in substantia nigra, and thus improve motor impairment of model mice,which may be mediated by the inhibition of Cdk5/p25 activity.
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ObjectiveTo determine the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism in Han ethnic patients with type 2 diabetes in Chenzhou area of Hunan province,and to assess the assoeiation between this polymorphism and diabetes.MethodsThis study was cross-sectional designed.Samples were taken by random sampling method from diabetes, prediabetes and euglycemia subjeers.ACE gene polymorphism I/D were examined by PCR.Genotype was classified as I1, ID, or DD based on positive or negative insertion/deletion allele.ResultsThis study showed significant differences of ages (X2 =32.09, P ＜0.01), body mass index (BMI) (X2 =16.10, P ＜0.01), family history (X2 =20.42, P ＜0.01) and serum triglyceride (F =21.289, P ＜0.01) among three groups, and diabetes group tended to have higher value.Frequency of genotype II, ID, DD were 72(56.3％) ,52(40.6％) and 4(3.1％) in diabetes, 64(64.0％) ,30(30.0％) and 6(6.0％) in pre-diabetes subjects, 81 (72.3％),29(25.9％)和 2(1.8％) in euglycemia subjects, consecutively.Chi-square analysis showed statistically significant association between ID + DD vs.Ⅱ genotype and diabetes (x2 = 6.68, P ＜ 0.05).Logistic regression analysis showed four variables that significantly influence to diabetes, namely ACE gene polymorphism, family history of diabetes, BMI, and serum triglyceride level.ConclusionsACE ID + DD genotype had significant relationship with diabetes in Chenzhou Han ethnic population, Hunan province, China.