Background Developmental and epileptic encephalopathy(DEE)is a group of rare inherited disorders characterized by intellectual disability,delayed development,epileptic seizures,and other related symptoms.DEE44 is caus...Background Developmental and epileptic encephalopathy(DEE)is a group of rare inherited disorders characterized by intellectual disability,delayed development,epileptic seizures,and other related symptoms.DEE44 is caused by mutations in the UBA5 gene,which encodes a ubiquitin-like protein involved in protein degradation and cell signaling.However,there is limited information on the genotype–phenotype correlation of DEE44,and its clinical features remain to be fully characterized.Case presentation We report a 12-month-old infant who presented with epileptic spastic seizures beginning at 4 months of age,accompanied by overall developmental delay,short stature,microcephaly,inability to hold his head upright,chasing vision,and high muscle tone in the extremities.Genetic findings showed compound heterozygous mutations of the UBA5 gene:NM_024818 c.562C>T(p.R188X)from the mother and NM_024818 c.214C>T(p.R72C)from the father.Conclusions This case report expands the clinical spectrum of DEE44 and highlights the importance of considering DEE44 in the differential diagnosis of developmental delay and epilepsy,even in the absence of classical symptoms suggestive of the condition.We hope that this case report will advance the understanding of DEE44 and improve the expertise of clinicians and early diagnose of this disease.展开更多
Angiotensin II Type 1 Receptor Autoantibodies(AT1-AA)as a functional receptor activator can persistently activate Angiotensin II Type 1 Receptor(AT1R)by causing AT1R non-desensitization which is one of the important p...Angiotensin II Type 1 Receptor Autoantibodies(AT1-AA)as a functional receptor activator can persistently activate Angiotensin II Type 1 Receptor(AT1R)by causing AT1R non-desensitization which is one of the important pathogenesis of preeclampsia(PE).However,the molecular mechanisms of AT1-AA results AT1R non-desensitization remain unknown.In order to explore the background molecular mechanisms of AT1R non-desensitization induced by AT1-AA,we construct dynamical models which are composed of control model(based on the body of healthy pregnant women)and experimental group models(based on the body of pregnant women with PE)in this paper.We also consider the effect of membrane fluidity on the reaction when building the dynamical models.In the experiment group models,we establish two models that caused AT1R non-desensitization:endocytosis disorder model and conformational change model.We write C++and MATLAB programs to do the data fitting.By comparing the data fitting results and analyzing the images of models and corresponding Bayesian information criterion(BIC)values,we conclude that conformational changes may be the key molecular mechanism of AT1R non-desensitization.展开更多
基金supported by Natural Science Foundation of Hainan Province of China(821RC1133).
文摘Background Developmental and epileptic encephalopathy(DEE)is a group of rare inherited disorders characterized by intellectual disability,delayed development,epileptic seizures,and other related symptoms.DEE44 is caused by mutations in the UBA5 gene,which encodes a ubiquitin-like protein involved in protein degradation and cell signaling.However,there is limited information on the genotype–phenotype correlation of DEE44,and its clinical features remain to be fully characterized.Case presentation We report a 12-month-old infant who presented with epileptic spastic seizures beginning at 4 months of age,accompanied by overall developmental delay,short stature,microcephaly,inability to hold his head upright,chasing vision,and high muscle tone in the extremities.Genetic findings showed compound heterozygous mutations of the UBA5 gene:NM_024818 c.562C>T(p.R188X)from the mother and NM_024818 c.214C>T(p.R72C)from the father.Conclusions This case report expands the clinical spectrum of DEE44 and highlights the importance of considering DEE44 in the differential diagnosis of developmental delay and epilepsy,even in the absence of classical symptoms suggestive of the condition.We hope that this case report will advance the understanding of DEE44 and improve the expertise of clinicians and early diagnose of this disease.
文摘Angiotensin II Type 1 Receptor Autoantibodies(AT1-AA)as a functional receptor activator can persistently activate Angiotensin II Type 1 Receptor(AT1R)by causing AT1R non-desensitization which is one of the important pathogenesis of preeclampsia(PE).However,the molecular mechanisms of AT1-AA results AT1R non-desensitization remain unknown.In order to explore the background molecular mechanisms of AT1R non-desensitization induced by AT1-AA,we construct dynamical models which are composed of control model(based on the body of healthy pregnant women)and experimental group models(based on the body of pregnant women with PE)in this paper.We also consider the effect of membrane fluidity on the reaction when building the dynamical models.In the experiment group models,we establish two models that caused AT1R non-desensitization:endocytosis disorder model and conformational change model.We write C++and MATLAB programs to do the data fitting.By comparing the data fitting results and analyzing the images of models and corresponding Bayesian information criterion(BIC)values,we conclude that conformational changes may be the key molecular mechanism of AT1R non-desensitization.
