Analysis of a family with early-onset dementia caused by a new mutation in the triggerring receptor expressing on myeloid cells 2 gene / 中华神经科杂志

Objective:To analyze the clinical phenotype, imaging characteristics and genetic characteristics of a family of early-onset dementia caused by a new mutation in the triggerring receptor expressing on myeloid cells 2 gene (TREM2).Methods:Clinical data were collected from a patient with early-onset dementia. Then whole exome sequencing was performed for the proband, followed by Sanger sequencing for the family members.Results:The clinical manifestations of the proband (a 49-year-old female) was personality changes, mental and behavioral abnormalities, memory loss, ataxia, and seizures. Whole-exon sequencing revealed a novel homozygous mutation in exon 2 of TREM2, namely c.154C>T (p.R52C) heterozygosity in four family members, and one patient with similar clinical manifestations was deceased. The proband′s brain magnetic resonance imaging showed bilateral frontotemporal atrophy, bilateral white matter hyperintensity, thin corpus callosum. No bone cysts of the hands and feet were found by digital radiographic imaging.Conclusions:A homozygous mutation in TREM2 gene was detected in a patient with frontotemporal dementia-like dementia, epilepsy, but without bone cysts. This mutation is probably pathogenic. This research highlights the importance of TREM2 gene mutation screening in early-onset dementia, especially in those with atypical presentations.

Clinical research of cerebral microbleeds in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy / 中华神经科杂志

Objective To investigate the frequency and location of cerebral microbleeds in cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) to understand the imaging and clinical features of the disease.Methods Cranial magnetic resonance imaging and susceptibility-weighted imaging were assessed in seven symptomatic CADASIL patients in People's Hospital of Zhengzhou University from 2014 to 2017.Imaging features and clinical significance of these patients were analyzed retrospectively.Results The seven patients were diagnosed by Notch3 gene detection.Mutations were found in exon 11 in four cases,and in exon 4 in three cases.All the seven patients with CADASIL had cerebral microbleeds,the number of which was 108 (4-36).The number of cerebral microbleeds was found to be higher in cortico-subcortical region than in any other regions.One of CADASIL patients with cerebral microbleeds had intracerebral hemorrhage located in external capsule.The patient with intracerebral hemorrhage had hypertension and multiple cerebral microbleeds.Conclusions Cerebral microbleeds are common imaging characteristics in symptomatic CADASIL,most of which locate in cortico-subcortical region.Cerebral hemorrhage is one of the clinical manifestations of CADASIL patients.

Fatal familial insomnia preliminarily diagnosed as frontotemporal dementia: a case report and literature review / 中华神经科杂志

Objective To explore the clinical,imaging,genetic features in a case of fatal familial insomnia (FFI),and review related literatures.Methods A case of middle-aged woman diagnosed as frontotemporal dementia based on the preliminary manifestation of abnormal mental behavior was reported.The clinical features,imaging characteristics,electroencephalogram and polysomnogram of the patient were analyzed,and the blood samples from the patient and some of her familial members were collected for the sequencing of prion protein gene (PRNP).Results This patient was a middle-aged woman,whose clinical manifestations were abnormal mental behavior,rapid progressive dementia and intractable insomnia,abnormal night sleep behavior and laryngeal stridor.Brain MRI indicated frontotemporal lobe atrophy.Non-sleep disturbance was observed in polysomnography.The cerebrospinal fluid was negative for 14-3-3 protein.The results of PRNP sequencing revealed that the mutation of gene D178N/129M was detected.Conclusions Detection of PRNP plays an important role in the diagnosis of FFI.Patients suspected of FFI in clinic should be detected for genetic testing.Whether the frontotemporal lobe atrophy was caused by FFI or concurrent with FFI remains to be further verified.

Clinical characteristics of four patients with primary intraspinal lymphoma / 中华神经科杂志

Objective To analyze clinical characteristics of four cases with primary intraspinal lymphoma to achieve early diagnosis of the disease.Methods Clinical data including the clinical presentation,imaging features and pathological characteristics of four patients diagnosed as primary intraspinal lymphoma confirmed surgically and pathologically from February 2014 to February 2017 in Henan Provincial People's Hospital were analyzed retrospectively,and literatures were reviewed.Results The major clinical manifestations of the primary intraspinal lymphoma were as following:persistent or intermittent waist (back) pain,accompanied with both lower limb weakness,dysfunction of motion,loss or disappearance of sensation,incontinence,followed by an acute progressive neurological function deterioration.The imaging showed a single fusiform shape or irregular lump.The T1 WI signal was equal or slightly lower,and T2WI showed equal or slightly higher signal,and the general signal uniform;The lump showed mild or moderate homogeneous enhancement.The group of four cases were B cell non-Hodgkin lymphoma confirmed by pathological biopsy.Conclusions The clinical and imaging features of primary intraspinal lymphoma are lack of specificity and are easy to be misdiaguosed.The diagnosis is mainly based on pathological biopsy.

Analysis of clinical, imaging and genetic mutations of 37 cases of cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy from 19 pedigrees / 中华神经科杂志

Objective To analyze the clinical, imaging characteristics and NOTCH3 mutations of cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy (CADASIL) in Henan, China.Methods CADASIL patients diagnosed by gene or biopsy in People′s Hospital of Zhengzhou University between 2012-2016 were recruited.Clinical and imaging features of these patients were analyzed retrospectively.The distribution of NOTCH3 gene mutations hotspots was described in Henan region at the same time.Results There were 37 patients from 19 families who were diagnosed as CADASIL by genetic testing or biopsy, 27 of whom had symptoms of CADASIL.Two families were confirmed by pathological examination and 17 by genetic testing.Of these 17 families, 13 mutations were found.Mutations in exon 11 were found in eight families, in exon 4 were detected in four families, and in exon 13 were found in two families.Mutation in exons 3, 8 and 20 was detected in one family respectively.Most patients presented with stroke and several presented with cognitive decline.Twelve patients had been attacked by risk factors.Magnetic resonance imaging (MRI) was performed on 22 patients.White-matter lesions were distributed in brain stem, basal ganglia, subcortical, temporal pole, external capsule.There were 19 patients with white-matter lesions in temporal pole and seven in capsula externa, showed as a high signal in T2WI.Conclusions CADASIL patients can be associated with risk factors.T2WI hyperintensities in the anterior temporal lobe were more common than that in the capsular external.Exon 11 and exon 4 were the hotspots for the NOTCH3 mutation in Henan patients.

CADASIL with clinical manifestations of baldness, lumbago and Parkinson's symptoms / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate a cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy (CADASIL) case with clinical manifestations of baldness, lumbago and Parkinson's symptoms.</p><p><b>METHODS</b>Clinical and imaging data of the patient were analyzed. The patient and his family members were also subjected to genetic testing.</p><p><b>RESULTS</b>The symptoms of the patient included recurrent stroke, dementia, and mood disturbance, in addition with lumbago, baldness and Parkinson's symptoms but no migraine. Cranial MRI of the patient showed bilateral symmetric leukoencephalopathy and multiple small subcortical lacunar infarcts. A point mutation in exon 11 of the NOTCH3 gene (R558C) was discovered in the proband and four asymptomatic relatives.</p><p><b>CONCLUSION</b>CADASIL is characterized by recurrent subcortical ischemic stroke, dementia, pseudobulbar palsy, and mood disturbance. Baldness, lumbago and Parkinson's symptoms may also be seen in such patients.</p>

Presenilin 1 gene mutation p.L226R in a Chinese early-onset familial Alzheimer's disease pedigree / 中华神经科杂志

Objective To analyze the clinical presentation , the mutation of the pathogenic genes and imaging features in a Chinese Han early-onset Alzheimer's disease pedigree.Methods A pedigree of Alzheimer's disease was collected.The DNA sequence of presenilin 1 (PSEN1), presenilin 2, micro-tubule associated protein tau ,β-amyloid precursor protein gene was analyzed , the clinical presentation , results of accessory examination , neuropsychological evaluation of the proband were investigated and the point mutations of some members of the family , 50 sporadic Alzheimer's disease patients , 50 normal controls were verified.Results The proband of the family appeared as language impairment , memory loss, personality change, repeated language, visuospatial impairment, mental and behavior disorder.The gene detection showed p.L226R mutation in the condon 226 in the exon 7 of PSEN1 gene of the proband and five other family members (Ⅲ1 ,Ⅲ2 ,Ⅲ4 ,Ⅲ6 ,Ⅲ7 ).The mother of the proband had the suspicious symptoms , and the sister and the brother of the proband had the similiar symptoms with the proband , all of whom died.Fifty sporadic Alzheimer'disease patients and 50 unrelated normal subjects did not have the mutation .The computed tomographic angiography showed that the brain blood vessels were normal and 18 F-fludeoxyglucose positron emission tomography (18F-FDG-PET) showed brain atrophy and hypometabolism in frontotemporal regions, parietal regions, hippocampal areas, however, the MRI, MRA and 18F-FDG-PET of the two mutation carriers (Ⅲ6 ,Ⅲ7 ) were all normal.Conclusion We reported a novel mutation in an early-onset Alzheimer's disease family presented as language impairment in the early stage of the disease , the p.L226R mutation of PSEN1, which may be a pathogenic mutation to cause the family's dementia.

R607C mutation of NOTCH3 gene and clinical features in 4 CADASIL families in Henan, China / 国际脑血管病杂志

Objective To investigate the NOTCH3 gene mutation and clinical features in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) families.Methods The clinical features of 4 CADASIL probands in Henan,China were analyzed retrospectively,and the incidences of other members in their families were investigated.The NOTCH3 gene mutations in the 3rd,4th,llth,and 18th exons were detected and the results were analyzed in the patients and some family members.Results Gene sequencing showed that 6 patients in 4 families and 1 mutant carrier had NOTCH3 gene R607C mutation in exon llth,they all met the clinical features of CADASIL.Three patients accompanied with vascular risk factors.The clinical stroke patients had unilateral limb weakness.All 5 patients with complete head MRIdata had thalamic infarction.Conclusions In the 4 CADASIL families of R607C mutation,the clinical features of 6 patients with CADASIL were similar,but there were individual differences in different family members.Imaging examination has important role in the diagnosis of CADASIL.The vascular risk factors,such as hyperte.