Clinical and Neuroimaging Characterization of Chinese Dementia Patients with PSEN1 and PSEN2 Mutations

2014 ◽  
Vol 39 (1-2) ◽  
pp. 32-40 ◽  
Author(s):  
Zhihong Shi ◽  
Ying Wang ◽  
Shuai Liu ◽  
Mengyuan Liu ◽  
Shuling Liu ◽  
...  
Keyword(s):  
Early Onset ◽  
Late Onset ◽  
Novel Mutation ◽  
Chinese Patients ◽  
Phenotypic Traits ◽  
Chinese Han ◽  
Risk Variants ◽  
Dementia Patients ◽  
Positron Emission ◽  
Neurodegenerative Dementia

Background: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two common forms of primary neurodegenerative dementia. Mutations in 3 genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset AD. Methods: We performed gene sequencing in PSEN1, PSEN2, and APP in 61 AD and 35 FTD Chinese patients. Amyloid load using 11C-labeled Pittsburgh compound B (11C-PIB) positron emission tomography (PET) and cerebral glucose metabolism using 18F-fludeoxyglucose PET were evaluated in patients carrying mutations. Results: We identified 1 known pathogenic PSEN1 (p.His163Arg, c.488A>G) mutation and 3 novel PSEN2 mutations in 6 patients. The novel mutation PSEN2 (p.His169Asn, c.505C>A) was identified in 1 patient with familial late-onset AD and in 1 sporadic FTD patient. The PSEN2 (p.Val214Leu, c.640G>T; p.Lys82Arg, c.245A>G) mutations were identified in 2 early-onset AD patients and 1 early-onset AD patient, respectively. Three patients with PSEN2 mutations were observed to have PIB retention on the cortex and striatum. One patient with the FTD phenotype was not observed to have PIB retention. Conclusion: PSEN2 mutations are common in the Chinese Han population with a history of AD and FTD. Pathogenic mutations or risk variants in the PSEN2 gene can influence both FTD and AD phenotypic traits and show variations in neuroimaging characterization. © 2014 S. Karger AG, Basel

scholarly journals Clinical and molecular characteristics of 69 Chinese patients with ornithine transcarbamylase deficiency

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Deyun Lu ◽  
Feng Han ◽  
Wenjuan Qiu ◽  
Huiwen Zhang ◽  
Jun Ye ◽  
...  
Keyword(s):  
Early Onset ◽  
Orotic Acid ◽  
Late Onset ◽  
Peak Plasma ◽  
Laboratory Data ◽  
Ornithine Transcarbamylase ◽  
Chinese Patients ◽  
Molecular Characteristics ◽  
Common Mutation ◽  
Ornithine Transcarbamylase Deficiency

Abstract Background This study aimed to describe the clinical and biochemical features of Chinese patients with ornithine transcarbamylase deficiency (OTCD), and to investigate the mutation spectrum of OTC gene and their potential correlation with phenotype. Methods Sixty-nine patients with OTCD were enrolled between 2004 and 2019. Clinical and laboratory data were reviewed retrospectively from medical records. Results Fifteen cases (13 males, 2 females) presented with early onset; 53 cases (21 males, 32 females) had late onset, and one female was asymptomatic. The median onset age was 1.5 years (range 1 day–56 years). Urine orotic acid levels were increased in all patients tested, while only 47.6% of patients showed decreased serum levels of citrulline. The peak plasma ammonia levels were higher in early-onset patients than in late-onset patients (P < 0.01). Fifty-four different mutations of OTC gene were identified and 18 of them were novel. R277W (10.6%) was the most common mutation, followed by G195R (4.6%) and A209V (3.0%). By June 2019, 41 patients had survived, 24 were deceased, and 4 were lost to follow-up. Among the survivors, 13 patients had received liver transplantation at a median age of 3 years, with a one-year survival rate of 100%. The mortality of OTCD is extremely high among patients with early onset (80.0% versus 24.5% in patients with late onset). Conclusions The evaluation of serum citrulline level is of limited value in diagnosis of OTCD, while urine orotic acid detection and genetic testing are more helpful.

GHRH-induced GH response in patients with senile dementia of the Alzheimer type

1988 ◽  
Vol 117 (3) ◽  
pp. 295-301 ◽  
Author(s):  
Ramón Cacabelos ◽  
Hisayoshi Niigawa ◽  
Yoshiaki Ikemura ◽  
Yuji Yanagi ◽  
Shigemi Tanaka ◽  
...  
Keyword(s):  
Early Onset ◽  
Late Onset ◽  
Senile Dementia ◽  
Elderly Subjects ◽  
Bioelectrical Activity ◽  
Alzheimer Type ◽  
Healthy Elderly ◽  
Dementia Patients ◽  
Ghrh Test ◽  
Senile Dementia Of The

Abstract. To clarify the functional state of the somatotropinergic system at the hypothalamo-hypophyseal level in senile dementia of the Alzheimer type, the GHRH test was performed in three groups of subjects: a) healthy elderly subjects; b) early onset senile dementia patients; and c) late onset senile dementia patients. Intravenous administration of GHRH(1–44)NH2 (100 μg) elicited a marked plasma GH response with a maximum peak (709.54 ± 259.0 pmol/l; P < 0.005) 60 min after injection in patients with early onset senile dementia, but no significant response was detected in the other two groups. Electroencephalographic recording showed that GHRH modifies brain bioelectrical activity, decreasing frequency (0.52 ± 0.15 Hz) and increasing amplitude (8.25 ± 4.5 μV) of the electroencephalogram basic rhythm. The evaluation of mental performance and behaviour with a battery of different tests for mental assessment revealed that GHRH induces transient clinical changes in psychomotor behaviour. According to these results, it seems likely that the somatostatin deficiency reported in senile dementia of the Alzheimer type may account for the enhanced GHRH-induced GH response observed in patients with early onset senile dementia. In consequence, the GHRH test might constitute a useful antemortem marker for senile dementia of the Alzheimer type if the present results can be replicated in early stages of the disease.

O4-04-02: Is Alzheimer's disease with early-onset different from late-onset?: A comparison using amyloid and glucose positron emission tomography

2012 ◽  
Vol 8 (4S_Part_17) ◽  
pp. P621-P621
Author(s):  
Timo Grimmer ◽  
Marion Ortner ◽  
Alexander Drzezga ◽  
Stefan Förster ◽  
Hans Förstl ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Early Onset ◽  
Late Onset ◽  
Emission Tomography ◽  
Positron Emission

scholarly journals Genetics and Clinical Characteristics of PPARγ Variant-Induced Diabetes in a Chinese Han Population

2021 ◽  
Vol 12 ◽  
Author(s):  
Siqian Gong ◽  
Xueyao Han ◽  
Meng Li ◽  
Xiaoling Cai ◽  
Wei Liu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Early Onset ◽  
Rare Variants ◽  
Good Choice ◽  
Chinese Patients ◽  
Chinese Han ◽  
Diabetes Group ◽  
Onset Type

ObjectivesPPARγ variants cause lipodystrophy, insulin resistance, and diabetes. This study aimed to determine the relationship between PPARγ genotypes and phenotypes and to explore the pathogenesis of diabetes beyond this relationship.MethodsPPARγ2 exons in 1,002 Chinese patients with early-onset type 2 diabetes (diagnosed before 40 years of age) were sequenced. The functions of variants were evaluated by in vitro assays. Additionally, a review of the literature was performed to obtain all reported cases with rare PPARγ2 variants to evaluate the characteristics of variants in different functional domains.ResultsSix (0.6%) patients had PPARγ2 variant-induced diabetes (PPARG-DM) in the early-onset type 2 diabetes group, including three with the p.Tyr95Cys variant in activation function 1 domain (AF1), of which five patients (83%) had diabetic kidney disease (DKD). Functional experiments showed that p.Tyr95Cys suppresses 3T3-L1 preadipocyte differentiation. A total of 64 cases with damaging rare variants were reported previously. Patients with rare PPARγ2 variants in AF1 of PPARγ2 had a lower risk of lipodystrophy and a higher rate of obesity than those with variants in other domains, as confirmed in patients identified in this study.ConclusionThe prevalence of PPARG-DM is similar in Caucasian and Chinese populations, and DKD was often observed in these patients. Patients with variants in the AF1 of PPARγ2 had milder clinical phenotypes and lack typical lipodystrophy features than those with variants in other domains. Our findings emphasize the importance of screening such patients via genetic testing and suggest that thiazolidinediones might be a good choice for these patients.

scholarly journals Novel MYO5B Mutation in Microvillous Inclusion Disease of Syrian Ancestry

2021 ◽  
pp. mcs.a006103
Author(s):  
Kamal Hassan ◽  
Amal Robay ◽  
Aljazi Al-Maraghi ◽  
Nuha Nimeri ◽  
Asmaa Azzam ◽  
...  
Keyword(s):  
Early Onset ◽  
Late Onset ◽  
Novel Mutation ◽  
Periodic Acid ◽  
Watery Diarrhea ◽  
Periodic Acid Schiff ◽  
Life Threatening ◽  
Different Populations ◽  
Cytoplasmic Accumulation ◽  
Microvillous Inclusion Disease

Microvillus inclusion disease (MVID, MIM♯ 251850), also known as congenital microvil-lus atrophy, was first described by Davidson et al. in 1978. It is a rare au-tosomal recessive disease that presents with an intractable life-threatening watery diarrhea either within the first days of life (early-onset form) or at several months of life (late-onset form) . The hallmarks of MVID are a lack of microvilli on the surface of villous enterocytes, occurrence of microvillous inclusions and the cytoplasmic accumulation of periodic acid-schiff-positive vesicles. In 2008, Muller et al showed that mutations in MYO5B (MIM ♯ 606540), en-coding the unconventional type Vb myosin motor protein, were associated with MVID in an ex-tended Turkish kindred. Since then, more mutations were described in different populations . In this report we describe a novel mutation in two unrelated Syrian patients with MVID.

scholarly journals Clinical and Molecular Characteristics of 69 Chinese Patients with Ornithine Transcarbamylase Deficiency

2020 ◽  
Author(s):  
Deyun Lu ◽  
Feng Han ◽  
Wenjuan Qiu ◽  
Huiwen Zhang ◽  
Jun Ye ◽  
...  
Keyword(s):  
Early Onset ◽  
Orotic Acid ◽  
Late Onset ◽  
Peak Plasma ◽  
Laboratory Data ◽  
Ornithine Transcarbamylase ◽  
Chinese Patients ◽  
Molecular Characteristics ◽  
Common Mutation ◽  
Ornithine Transcarbamylase Deficiency

Abstract Background: This study aimed to describe the clinical and biochemical features of Chinese patients with ornithine transcarbamylase deficiency (OTCD), and to investigate the mutation spectrum of OTC gene and their potential correlation with phenotype.Methods: Sixty-nine patients with OTCD were enrolled between 2004 and 2019. Clinical and laboratory data were reviewed retrospectively from medical records. Results: Fifteen cases (13 males, 2 females) presented with early onset; 53 cases (21 males, 32 females) had late onset, and one female was asymptomatic. The median onset age was 1.5 years (range, 1 day-56 years). Urine orotic acid levels were increased in all patients tested, while only 47.6% of patients showed decreased serum levels of citrulline. The peak plasma ammonia levels were higher in early-onset patients than in late-onset patients (P < 0.01). Fifty-four different mutations of OTC gene were identified and 18 of them were novel. R277W (10.6%) was the most common mutation, followed by G195R (4.6%) and A209V (3.0%). By June 2019, 41 patients had survived, 24 were deceased, and 4 were lost to follow-up. Among the survivors, 13 patients had received liver transplantation at a median age of 3 years, with a one-year survival rate of 100%. The mortality of OTCD is extremely high among patients with early onset (80.0% versus 24.5% in patients with late onset).Conclusions: The evaluation of serum citrulline level is of limited value in diagnosis of OTCD, while urine orotic acid detection and genetic testing are more helpful.

scholarly journals HSPA1L rs1061581 polymorphism is associated with the risk of preeclampsia in Han Chinese women

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Jinbao Zong ◽  
Yan Lin ◽  
Qingwu Tian ◽  
Xin Zhao ◽  
Kaiqiu Chu ◽  
...  
Keyword(s):  
Early Onset ◽  
Late Onset ◽  
Chinese Women ◽  
Stress Protein ◽  
Han Chinese ◽  
Chinese Han ◽  
Allelic Discrimination ◽  
Allelic Frequencies ◽  
Polymerase Chain ◽  
Risk Of Preeclampsia

Abstract Preeclampsia (PE) is an excessive systemic inflammation response with dysfunction of endothelial. As a stress protein, heat shock protein 70 (HSP70) plays a pivotal role in protecting cells against apoptosis, oxidative damage and genetic damage. In humans, three genes encode members of the HSP70 class: HSPA1A, HSPA1B and HSPA1L. Our study was to investigate the association between genetic variations of HSPA1L and the susceptibility for PE in Chinese Han population. The polymorphisms of rs2227956, rs1043618 and rs1061581 in HSPA1L were genotyped by TaqMan allelic discrimination real time polymerase chain reaction (PCR) in 929 PE patients and 1024 healthy pregnant women. Statistic difference of the genotypic and allelic frequencies were found in HSPA1L rs1061581 between PE patients and controls (χ2 = 29.863, P &lt; 0.001 by genotype; χ2 = 27.298, P &lt; 0.001, OR = 1.874, 95%CI 1.476–2.379 by allele) and HSPA1L rs1061581 A alleles occurred more frequently in PE patients compared with healthy controls (PE vs. controls 10.28% vs. 5.76%). Furthermore, we divided the PE cases into early-onset/late-onset PE and mild/severe PE subgroups and found statistical differences in genotypic and allelic frequencies of the HSPA1L rs1061581 between early-onset PE, late-onset PE, mild PE, severe PE and controls, respectively. Moreover, HSPA1L rs1061581 A alleles were more frequent in early-onset PE, late-onset PE, mild PE and severe PE than controls respectively. Therefore, we concluded that HSPA1L rs1061581 polymorphism is associated with the risk of PE in Han Chinese women and A alleles may play a role in the susceptibility for PE.

scholarly journals Analysis of Risk Factors for First Seizure after Stroke in Chinese Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Guoqing Wang ◽  
Haiyan Jia ◽  
Chunfu Chen ◽  
Senyang Lang ◽  
Xinfeng Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Subarachnoid Hemorrhage ◽  
Early Onset ◽  
Late Onset ◽  
Chinese Patients ◽  
Onset Seizure ◽  
Large Lesion ◽  
Related Risk ◽  
Independent Risk Factors ◽  
Cortical Involvement

The aim of this study is to assess related risk factors and predict early- and late-onset seizure after first-ever stroke. A total of 2474 consecutive patients with initial stroke in China from 1997 to 2007 were retrospectively investigated, in which, 24 clinical and radiological indexes were used for evaluation. Odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression. A total of 232 (11.1%) of patients developed seizures during a mean follow-up period of 18 months, with 123 experiencing early-onset and 109 late-onset seizure. The independent risk factors for early-onset seizure were large lesion (OR=9.36), subarachnoid hemorrhage (OR=5.28), initial hyponatremia (OR=2.10), and cortical involvement (OR=1.33). The independent risk factors for late-onset seizure were cortical involvement (OR=11.84) and large lesion (OR=1.87). These results demonstrated that the risk factors for early seizure after stroke are large lesion, subarachnoid hemorrhage, and cortical involvement. Surprisingly, hyponatremia also predicts seizure in stroke patients. Cortical involvement is a major risk factor for late-onset seizure after stroke.

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