BACKGROUND IFIH1 is a protein-coding gene.Disorders associated with IFIH1 include Aicardi-Goutières syndrome(AGS)type 7 and Singleton-Merten syndrome type 1.Related pathways include RIG-I/MDA5-mediated induction ...BACKGROUND IFIH1 is a protein-coding gene.Disorders associated with IFIH1 include Aicardi-Goutières syndrome(AGS)type 7 and Singleton-Merten syndrome type 1.Related pathways include RIG-I/MDA5-mediated induction of the interferon(IFN)-α/βpathway and the innate immune system.AGS type 7 is an autosomal dominant inflammatory disorder characterized by severe neurological impairment.In infancy,most patients present with psychomotor retardation,axial hypotonia,spasticity,and brain imaging changes Laboratory assessments showed increased IFN-αactivity with upregulation of IFN signaling and IFN-stimulated gene expression.Some patients develop normally in the early stage,and then have episodic neurological deficits.CASE SUMMARY The 5-year-old girl presented with postpartum height and weight growth retardation,language retardation,brain atrophy,convulsions,and growth hormone deficiency.DNA samples were obtained from peripheral blood from the child and her parents for whole-exome sequencing and test of genome-wide copy number variation.Heterozygous mutations in the IFIH1 gene were found.Physical examination at admission found that language development was delayed,the reaction to name calling was average,there was no communication with people,but there was eye contact,no social smile,and no autonomous language.However,the child had rich gesture language and body language,could understand instructions,had bad temper.When she wants to achieve something,she starts crying or shouting.Cardiopulmonary examination showed no obvious abnormality,and abdominal examination was normal.Bilateral muscle strength and muscle tone were symmetrical and slightly decreased.Physiological reflexes exist,but pathological reflexes were not elicited.CONCLUSION We reported the clinical characteristics of a Chinese child with a clinical diagnosis of AGS type 7,which expanded the mutational spectrum of the IFIH1 gene.展开更多
Aicardi-Goutières syndrome (AGS) is a rare inflammatory encephalopathy mimicking in utero acquired viral infection. Cardinal findings comprise leukodystrophy, basal ganglia calcifications and cerebral atrophy alo...Aicardi-Goutières syndrome (AGS) is a rare inflammatory encephalopathy mimicking in utero acquired viral infection. Cardinal findings comprise leukodystrophy, basal ganglia calcifications and cerebral atrophy along with cerebrospinal fluid lymphocytosis and elevated interferon-α. In the majority of cases AGS is inherited as an autosomal recessive trait and caused by mutations in six genes including RNASEH2A, RNASEH2B, RNASEH2C, TREX1, SAMHD1 and ADAR1, all of which encode enzymes acting on nucleic acid species. Most patients present with first neurological signs in early infancy and experience severe global developmental delay. Here, we report on the unusual divergent phenotype of two siblings who both carry the most frequent AGS causing p.A177T (c.529G > A) RNASEH2B mutation in the homozygous state. While one sibling showed a typical AGS presentation with early onset and severe statomotor and mental impairment, the older sibling was intellectually completely normal. She was only diagnosed because of mild spasticity of the legs and serological signs of autoimmunity. These findings highlight the phenotypic variability of AGS and suggest that AGS may be underdiagnosed among children with mild cerebral palsy.展开更多
Background: Individuals with 22q11.2DS, a genetic subtype of Schizophrenia, respond as well to clozapine as those with other forms of Schizophrenia. It has been reported that serious and rare adverse events like seizu...Background: Individuals with 22q11.2DS, a genetic subtype of Schizophrenia, respond as well to clozapine as those with other forms of Schizophrenia. It has been reported that serious and rare adverse events like seizures, and myocarditis have been associated with clozapine treatment in this population. To the best of our knowledge, the incidence of neuroleptic malignant syndrome (NMS) as an adverse effect of antipsychotic use in patients with this disorder has not yet been reported. Aim: In this article, we discuss a case of clozapine-induced NMS and subsequent re-challenge in a patient with 22q11.2DS-associated schizophrenia. The aim of this study is to accumulate scientific data about rare presentations, and serve as a major educational tool, and highlight the unique challenges faced when using clozapine in a patient with DiGeorge Syndrome. Methods: This is a descriptive case report of a patient encountered in the inpatient unit which includes retrospective review of the patient’s electronic medical record and a literature review of antipsychotic medications-induced NMS. Conclusion: This study demonstrates a successful re-challenge with clozapine after the patient developed NMS and seizures during the initial treatment and also highlights how, in addition to drug level monitoring, considering pharmacogenetic testing early in treatment might help minimize adverse drug reactions in individuals with known genetic disorders such as 22q11.2DS.展开更多
BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndrome...BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndromes called Pi-Xu-Shi-Yun(PXSY)and Da-Chang-Shi-Re(DCSR).The relationships among gut microbiota,TCM syndromes,and UC pathogenesis have not been well investigated.AIM To investigate the role of gut microbiota in UC and the distinction of microbiota dysbiosis between PXSY and DCSR syndromes.METHODS From May 2015 to February 2016,UC patients presenting to LongHua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study.Fresh stool specimens of UC patients with PXSY or DCSR were collected.The feces of the control group came from the health examination population of Longhua Hospital.The composition of gut bacterial communities in stool samples was determined by the pyrosequencing of 16S ribosomal RNA.The high-throughput sequencing reads were processed with QIIME,and biological functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.RESULTS The composition of gut bacterial communities in 93 stool samples(30 healthy controls,32 patients with PXSY syndrome,and 31 patients with DCSR syndrome)was determined by the pyrosequencing of 16S ribosomal RNA.Beta diversity showed that the composition of the microbiota was different among the three groups.At the family level,Porphyromonadaceae,Rikeneliaceae,and Lachnospiraceae significantly decreased while Enterococcus,Streptococcus,and other potential pathogens significantly increased in UC patients compared to healthy subjects.At the genus level,Parabacteroides,Dorea,and Ruminococcus decreased while Faeca-libacterium showed increased abundance in UC compared to healthy controls.Five differential taxa were identified between PXSY and DCSR syndromes.At the genus level,a significantly increased abundance of Streptococcus was observed in DCSR patients,while Lachnoclostridium increased in PXSY patients.The differential functional pathways of the gut microbiome between the PXSY and DCSR groups mainly included lipid metabolism,immunity,and the metabolism of polypeptides.CONCLUSION Our study suggests that the gut microbiota contributes to the distinction between the two TCM syndromes of UC.展开更多
BACKGROUND: Hepatic artery thrombosis (HAT) is a frequent complication following liver transplantation, but it is rarely caused by arcuate ligament compression of the celiac artery. This article mainly describes our e...BACKGROUND: Hepatic artery thrombosis (HAT) is a frequent complication following liver transplantation, but it is rarely caused by arcuate ligament compression of the celiac artery. This article mainly describes our experience in managing a patient with celiac artery stenosis and HAT after liver transplantation. METHODS: A 44-year-old man with a 15-year history of hepatitis B was admitted to our hospital for hepatocellular carcinoma. Before the operatiori, he received transarterial chemoembolization once, and pretransplant MR angiography indicated a suspected stenosis at the initiation of the celiac artery, while color Doppler showed normal blood flow in the arterial system. In this case, orthotopic liver transplantation was performed for radical cure of hepatocellular carcinoma. However, B-ultrasonography detected poor blood flow in the intra- and extra-hepatic artery on the first posttransplant day, and during exploratory laparotomy a thrombus was found in the hepatic artery. Thus, re-transplantation was conducted with a bypass between the graft hepatic artery and the recipient abdominal aorta with the donor's splenic artery. RESULTS: The patient made an uneventful recovery and color Doppler showed good blood flow in the artery and portal system. Histology confirmed extensive thrombosis in the left and right hepatic artery of the explanted graft, indicating HAT. CONCLUSIONS: Although HAT caused by celiac trunk compression is rarely reported in liver transplantation, the diagnosis should be considered in patients with pretransplant hepatic artery stenosis on angiography and abnormal blood flow on B-ultrasonography. Once HAT is formed, treatment such as thrombectomy or retransplantation should be performed as early as possible.展开更多
文摘BACKGROUND IFIH1 is a protein-coding gene.Disorders associated with IFIH1 include Aicardi-Goutières syndrome(AGS)type 7 and Singleton-Merten syndrome type 1.Related pathways include RIG-I/MDA5-mediated induction of the interferon(IFN)-α/βpathway and the innate immune system.AGS type 7 is an autosomal dominant inflammatory disorder characterized by severe neurological impairment.In infancy,most patients present with psychomotor retardation,axial hypotonia,spasticity,and brain imaging changes Laboratory assessments showed increased IFN-αactivity with upregulation of IFN signaling and IFN-stimulated gene expression.Some patients develop normally in the early stage,and then have episodic neurological deficits.CASE SUMMARY The 5-year-old girl presented with postpartum height and weight growth retardation,language retardation,brain atrophy,convulsions,and growth hormone deficiency.DNA samples were obtained from peripheral blood from the child and her parents for whole-exome sequencing and test of genome-wide copy number variation.Heterozygous mutations in the IFIH1 gene were found.Physical examination at admission found that language development was delayed,the reaction to name calling was average,there was no communication with people,but there was eye contact,no social smile,and no autonomous language.However,the child had rich gesture language and body language,could understand instructions,had bad temper.When she wants to achieve something,she starts crying or shouting.Cardiopulmonary examination showed no obvious abnormality,and abdominal examination was normal.Bilateral muscle strength and muscle tone were symmetrical and slightly decreased.Physiological reflexes exist,but pathological reflexes were not elicited.CONCLUSION We reported the clinical characteristics of a Chinese child with a clinical diagnosis of AGS type 7,which expanded the mutational spectrum of the IFIH1 gene.
基金supported by the Deutsche Forschungsgemeinschaft(VT 421/2-1 to V.T.,LE 1074/4-1 to M.L.-K.)a MeDDrive grant of the Medical Faculty,TU Dresdensupport by the Deutsche Forschungsgemeinschaft and the Open Access Publication Funds of the TU Dresden
文摘Aicardi-Goutières syndrome (AGS) is a rare inflammatory encephalopathy mimicking in utero acquired viral infection. Cardinal findings comprise leukodystrophy, basal ganglia calcifications and cerebral atrophy along with cerebrospinal fluid lymphocytosis and elevated interferon-α. In the majority of cases AGS is inherited as an autosomal recessive trait and caused by mutations in six genes including RNASEH2A, RNASEH2B, RNASEH2C, TREX1, SAMHD1 and ADAR1, all of which encode enzymes acting on nucleic acid species. Most patients present with first neurological signs in early infancy and experience severe global developmental delay. Here, we report on the unusual divergent phenotype of two siblings who both carry the most frequent AGS causing p.A177T (c.529G > A) RNASEH2B mutation in the homozygous state. While one sibling showed a typical AGS presentation with early onset and severe statomotor and mental impairment, the older sibling was intellectually completely normal. She was only diagnosed because of mild spasticity of the legs and serological signs of autoimmunity. These findings highlight the phenotypic variability of AGS and suggest that AGS may be underdiagnosed among children with mild cerebral palsy.
文摘Background: Individuals with 22q11.2DS, a genetic subtype of Schizophrenia, respond as well to clozapine as those with other forms of Schizophrenia. It has been reported that serious and rare adverse events like seizures, and myocarditis have been associated with clozapine treatment in this population. To the best of our knowledge, the incidence of neuroleptic malignant syndrome (NMS) as an adverse effect of antipsychotic use in patients with this disorder has not yet been reported. Aim: In this article, we discuss a case of clozapine-induced NMS and subsequent re-challenge in a patient with 22q11.2DS-associated schizophrenia. The aim of this study is to accumulate scientific data about rare presentations, and serve as a major educational tool, and highlight the unique challenges faced when using clozapine in a patient with DiGeorge Syndrome. Methods: This is a descriptive case report of a patient encountered in the inpatient unit which includes retrospective review of the patient’s electronic medical record and a literature review of antipsychotic medications-induced NMS. Conclusion: This study demonstrates a successful re-challenge with clozapine after the patient developed NMS and seizures during the initial treatment and also highlights how, in addition to drug level monitoring, considering pharmacogenetic testing early in treatment might help minimize adverse drug reactions in individuals with known genetic disorders such as 22q11.2DS.
基金Supported by the National Natural Science Foundation of China,No.81704009,No.81873253,No.81573892,and No.81770571the Project of Shanghai Municipal Health and Family Planning Commission,No.201640122
文摘BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndromes called Pi-Xu-Shi-Yun(PXSY)and Da-Chang-Shi-Re(DCSR).The relationships among gut microbiota,TCM syndromes,and UC pathogenesis have not been well investigated.AIM To investigate the role of gut microbiota in UC and the distinction of microbiota dysbiosis between PXSY and DCSR syndromes.METHODS From May 2015 to February 2016,UC patients presenting to LongHua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study.Fresh stool specimens of UC patients with PXSY or DCSR were collected.The feces of the control group came from the health examination population of Longhua Hospital.The composition of gut bacterial communities in stool samples was determined by the pyrosequencing of 16S ribosomal RNA.The high-throughput sequencing reads were processed with QIIME,and biological functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.RESULTS The composition of gut bacterial communities in 93 stool samples(30 healthy controls,32 patients with PXSY syndrome,and 31 patients with DCSR syndrome)was determined by the pyrosequencing of 16S ribosomal RNA.Beta diversity showed that the composition of the microbiota was different among the three groups.At the family level,Porphyromonadaceae,Rikeneliaceae,and Lachnospiraceae significantly decreased while Enterococcus,Streptococcus,and other potential pathogens significantly increased in UC patients compared to healthy subjects.At the genus level,Parabacteroides,Dorea,and Ruminococcus decreased while Faeca-libacterium showed increased abundance in UC compared to healthy controls.Five differential taxa were identified between PXSY and DCSR syndromes.At the genus level,a significantly increased abundance of Streptococcus was observed in DCSR patients,while Lachnoclostridium increased in PXSY patients.The differential functional pathways of the gut microbiome between the PXSY and DCSR groups mainly included lipid metabolism,immunity,and the metabolism of polypeptides.CONCLUSION Our study suggests that the gut microbiota contributes to the distinction between the two TCM syndromes of UC.
文摘BACKGROUND: Hepatic artery thrombosis (HAT) is a frequent complication following liver transplantation, but it is rarely caused by arcuate ligament compression of the celiac artery. This article mainly describes our experience in managing a patient with celiac artery stenosis and HAT after liver transplantation. METHODS: A 44-year-old man with a 15-year history of hepatitis B was admitted to our hospital for hepatocellular carcinoma. Before the operatiori, he received transarterial chemoembolization once, and pretransplant MR angiography indicated a suspected stenosis at the initiation of the celiac artery, while color Doppler showed normal blood flow in the arterial system. In this case, orthotopic liver transplantation was performed for radical cure of hepatocellular carcinoma. However, B-ultrasonography detected poor blood flow in the intra- and extra-hepatic artery on the first posttransplant day, and during exploratory laparotomy a thrombus was found in the hepatic artery. Thus, re-transplantation was conducted with a bypass between the graft hepatic artery and the recipient abdominal aorta with the donor's splenic artery. RESULTS: The patient made an uneventful recovery and color Doppler showed good blood flow in the artery and portal system. Histology confirmed extensive thrombosis in the left and right hepatic artery of the explanted graft, indicating HAT. CONCLUSIONS: Although HAT caused by celiac trunk compression is rarely reported in liver transplantation, the diagnosis should be considered in patients with pretransplant hepatic artery stenosis on angiography and abnormal blood flow on B-ultrasonography. Once HAT is formed, treatment such as thrombectomy or retransplantation should be performed as early as possible.
