This study is a report on one 59-year-old male patient with hereditary multi-infarct dementia who came from a family with a positive family history of this disease. The patient primarily presented with dizziness accom...This study is a report on one 59-year-old male patient with hereditary multi-infarct dementia who came from a family with a positive family history of this disease. The patient primarily presented with dizziness accompanied by vertigo and a positive Romberg's sign. Skull magnetic resonance images showed lacunar infarction in bilateral temporal lobes, bilateral basal ganglias, periventricular white matter and semioval center, and ischemic focus accompanied by white matter degeneration, exhibiting senile morphological brain changes. No abnormalities were observed by skull magnetic resonance angiography. Gene detection further confirmed that there was Arg607Cys heterozygous mutation in exon 11 of the Notch3gene. No other mutations in exons were detected.展开更多
Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditar5 small artery disease caused by NOTCH3 gene mutation. We performed enhanced depth imag...Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditar5 small artery disease caused by NOTCH3 gene mutation. We performed enhanced depth imaging optical coherence tomography (EDI-OCT) to evaluate the retinal vessel changes in CADASIL patients and assessed their consonance with brain magnetic resonance imaging (MPRI) findings. Methods: Of 27 genetically confirmed patients and an equal number of controls were recruited at the Peking University First ttospital from January 2015 to August 2016. All patients underwent 7T-MRI of the brain. Fazekas score, number of small infarcts and microblecds were evaluated. All patients and controls underwent EDI-OCT to measure subtbveal choroidal thickness (SFCT), inner and outer diameters as well as arterial and venous wall thickness, and arterial venous ratio of the inner (AVRin) and outer diameters (AVRout). The relation between retinal vessel changes and Fazekas scores, numbers of small infarcts, or microbleeds was analyzed. Paired t-test was used to compare the SFCT and retinal vessel measurement data between patients and controls. Spearman's correlation was used to investigmc the correlation between retinal vessel changes and MRI lesions. Results: In CADASI L patients, mean SFCT (268.37 ± 46.50 μm) and mean arterial inner diameter (93.46 ± 9.70 gin) were signilicantly lower than that in controls (P 〈 0.00 ), P = 0.048, respectively). Mean arterial outer diameter ( 131.74 ± 10.87 μm), venous inner ( 128.99 ± 13.62 μm) and outer diameter ( 164.82 ±14.77 μm), and mean arterial ( 19.13 ±1.85 μm) and venous ( 17.91 ±2.76 μm) wall thickness were significantly higher than that in controls (P = 0.023, P 0.004, P 〈 0.001, P 〈 0.001, respectively). Arterial inner diameter (r= - 0.39, P 0.044)] AVRin (r -0.65, P 〈 0.001), and AVR,, (r =0.56, P - 0.002) showed a negative correlation with the number of small infarcts. Venous inner diameter (rs=0.46, P= 0.016) showed a positive correlation with the number of small infarcts. Venous inner diameter (r 0.59, P = 0.002), outer diameter (rs=0.47, P= 0.017), showed a positive correlation with the number of cerebral microbleeds (CM Bs). AVRin (r =0.52, P = 0.007) and AVRout (r = -0.40, P =0.048) showed a negative correlation with the number of CMBs. Conclusions: Measurement of retinal vessels using EDI-OCT correlates moderately well with MRI parameters. EDI-OCT might bc a useful evaluation tool for CADASIL patients.展开更多
Background:The etiology of pulmonary arterial hypertension associated with congenital heart disease(PAHCHD)is complicated and the phenotype is heterogeneous.Genetic defects of NOTCH3 were associated withcerebral disea...Background:The etiology of pulmonary arterial hypertension associated with congenital heart disease(PAHCHD)is complicated and the phenotype is heterogeneous.Genetic defects of NOTCH3 were associated withcerebral disease and pulmonary hypertension.However,the relationship between NOTCH3 mutations and theclinical phenotype has not been reported in CHD-PAH.Methods:We eventually enrolled 142 PAH-CHD patientsfrom Fuwai Hospital.Whole exome sequencing(WES)was performed to screen the rare deleterious variants ofNOTCH3 gene.Results:This PAH-CHD cohort included 43(30.3%)men and 99(69.7%)women with the meanage 29.8±10.9 years old.The pathogenic or likely pathogenic mutations of NOTCH3 were identified in five cases.Patients 2,5,8 and 11 carried the same NOTCH3 mutation c.1630C>T(pArg544Cys),which is the hot-spotmutation for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL).Patient 3 carried the NOTCH3 mutation p.Arg75Gln that has also been reported to be associatedwith the CADASIL.Patients 2,5,8,11 took the examination of the cerebral magnetic resonance imaging(MRI)and confirmed the phenotype of CADASIL.Conclusions:We first reported the NOTCH3 rare mutationsand CADASIL phenotypes in CHD-PAH patients.The NOTCH3 rare variants were with a relatively high positiverate and CADASIL phenotypes were likely enriched in PAH-CHD patients.The preoperative neurological examinationmight be recommended for PAH-CHD patients to determine the surgical contraindications and reduceintraoperative neurological complications.展开更多
基金the National Natural Science Foundation of China,No,31100783Fengxian District Science Technology Commission Foundation of Shanghai,No.2010-101101
文摘This study is a report on one 59-year-old male patient with hereditary multi-infarct dementia who came from a family with a positive family history of this disease. The patient primarily presented with dizziness accompanied by vertigo and a positive Romberg's sign. Skull magnetic resonance images showed lacunar infarction in bilateral temporal lobes, bilateral basal ganglias, periventricular white matter and semioval center, and ischemic focus accompanied by white matter degeneration, exhibiting senile morphological brain changes. No abnormalities were observed by skull magnetic resonance angiography. Gene detection further confirmed that there was Arg607Cys heterozygous mutation in exon 11 of the Notch3gene. No other mutations in exons were detected.
基金This study was supported by grants from the National Key Research and Development Program of China (No. 2016YFC1300600), National Natural Science Foundation of China (No. 81471185), and National Science and Technology Major Project (No. 2011 ZX09307-001-07).
文摘Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditar5 small artery disease caused by NOTCH3 gene mutation. We performed enhanced depth imaging optical coherence tomography (EDI-OCT) to evaluate the retinal vessel changes in CADASIL patients and assessed their consonance with brain magnetic resonance imaging (MPRI) findings. Methods: Of 27 genetically confirmed patients and an equal number of controls were recruited at the Peking University First ttospital from January 2015 to August 2016. All patients underwent 7T-MRI of the brain. Fazekas score, number of small infarcts and microblecds were evaluated. All patients and controls underwent EDI-OCT to measure subtbveal choroidal thickness (SFCT), inner and outer diameters as well as arterial and venous wall thickness, and arterial venous ratio of the inner (AVRin) and outer diameters (AVRout). The relation between retinal vessel changes and Fazekas scores, numbers of small infarcts, or microbleeds was analyzed. Paired t-test was used to compare the SFCT and retinal vessel measurement data between patients and controls. Spearman's correlation was used to investigmc the correlation between retinal vessel changes and MRI lesions. Results: In CADASI L patients, mean SFCT (268.37 ± 46.50 μm) and mean arterial inner diameter (93.46 ± 9.70 gin) were signilicantly lower than that in controls (P 〈 0.00 ), P = 0.048, respectively). Mean arterial outer diameter ( 131.74 ± 10.87 μm), venous inner ( 128.99 ± 13.62 μm) and outer diameter ( 164.82 ±14.77 μm), and mean arterial ( 19.13 ±1.85 μm) and venous ( 17.91 ±2.76 μm) wall thickness were significantly higher than that in controls (P = 0.023, P 0.004, P 〈 0.001, P 〈 0.001, respectively). Arterial inner diameter (r= - 0.39, P 0.044)] AVRin (r -0.65, P 〈 0.001), and AVR,, (r =0.56, P - 0.002) showed a negative correlation with the number of small infarcts. Venous inner diameter (rs=0.46, P= 0.016) showed a positive correlation with the number of small infarcts. Venous inner diameter (r 0.59, P = 0.002), outer diameter (rs=0.47, P= 0.017), showed a positive correlation with the number of cerebral microbleeds (CM Bs). AVRin (r =0.52, P = 0.007) and AVRout (r = -0.40, P =0.048) showed a negative correlation with the number of CMBs. Conclusions: Measurement of retinal vessels using EDI-OCT correlates moderately well with MRI parameters. EDI-OCT might bc a useful evaluation tool for CADASIL patients.
基金Grant 81425002 from the National Science Fund for Distinguished Young ScholarsGrants 81670052,and 81870050 from the National Natural Science Foundation of ChinaGrant 2018ZX09711001-003-012 from the Drug Innovation Major Project,CAMS Fund for Key Laboratory of Pulmonary Vascular Medicine(2017PT32016).
文摘Background:The etiology of pulmonary arterial hypertension associated with congenital heart disease(PAHCHD)is complicated and the phenotype is heterogeneous.Genetic defects of NOTCH3 were associated withcerebral disease and pulmonary hypertension.However,the relationship between NOTCH3 mutations and theclinical phenotype has not been reported in CHD-PAH.Methods:We eventually enrolled 142 PAH-CHD patientsfrom Fuwai Hospital.Whole exome sequencing(WES)was performed to screen the rare deleterious variants ofNOTCH3 gene.Results:This PAH-CHD cohort included 43(30.3%)men and 99(69.7%)women with the meanage 29.8±10.9 years old.The pathogenic or likely pathogenic mutations of NOTCH3 were identified in five cases.Patients 2,5,8 and 11 carried the same NOTCH3 mutation c.1630C>T(pArg544Cys),which is the hot-spotmutation for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL).Patient 3 carried the NOTCH3 mutation p.Arg75Gln that has also been reported to be associatedwith the CADASIL.Patients 2,5,8,11 took the examination of the cerebral magnetic resonance imaging(MRI)and confirmed the phenotype of CADASIL.Conclusions:We first reported the NOTCH3 rare mutationsand CADASIL phenotypes in CHD-PAH patients.The NOTCH3 rare variants were with a relatively high positiverate and CADASIL phenotypes were likely enriched in PAH-CHD patients.The preoperative neurological examinationmight be recommended for PAH-CHD patients to determine the surgical contraindications and reduceintraoperative neurological complications.