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Objective:To analyze the clinical phenotypic characteristics and therapeutic effect of cutaneous anthrax patients in Ningxia Hui Autonomous Region (referred to as Ningxia).Methods:A retrospective analysis was conducted on the medical records of 76 confirmed patients with cutaneous anthrax in three prefecture level hospitals in Ningxia from 2017 to 2022. According to the length of hospital treatment, the patients were divided into a disease course ≥7 d group ( n = 54) and a disease course < 7 d group ( n = 22), and the clinical phenotypic characteristics (including patients' general condition, clinical symptoms, and laboratory tests) and therapeutic effects (the effect of hormone use and the choice of antibiotics) of the two groups were analyzed by methods such as χ 2 test. Results:Among 76 patients with cutaneous anthrax, males accounted for 81.6% (62/76) and females accounted for 18.4% (14/76), with a statistically significant difference in gender composition ratio (χ 2 = 5.71, P = 0.017). Among the 76 patients, 73 caces (96.1%) achieved clinical cure. There was no statistically significant differences between the groups in clinical characteristics such as temperature, pain, pruritus, edema, and site of onset ( P > 0.05). There were no statistically significant differences between groups in laboratory tests such as blood routine, liver function, hypersensitive C-reactive protein, secretion culture, PCR, etc. ( P > 0.05). There was a statistically significant difference in the distribution of edema resolution time between patients using hormone or not (χ 2 = 17.01, P = 0.002). There was no statistically significant difference in the distribution of disease course between different antibiotic treatment regimens when using hormone (χ 2 = 5.43, P = 0.143). There was a statistically significant difference in the distribution of disease course between different antibiotic treatment regimens when no using hormone (χ 2 = 108.46, P < 0.001). Conclusions:The majority of cutaneous anthrax patients in Ningxia from 2017 to 2022 are males. Early use of hormones can affect the duration of edema in patients. For patients who have not received hormone therapy, different treatment plans can affect the patient's course of disease.
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Dravet syndrome is a rare and severe developmental epileptic encephalopathy with variable clinical phenotypes.Dravet syndrome is difficult to diagnose and treat, and related comorbidities have a profound impact on the long-term quality of life of patients and their parents.SCN1A is the main pathogenic gene of Dravet syndrome, and SCN1A mutations are found in more than 85% of the patients.In recent years, with the development of genetic testing technology and the accumulation of cases, the understanding of the characteristics of epileptic seizures, comorbidities and SCN1A gene mutation characteristics in Dravet syndrome has gradually deepened.In addition to conventional antiepileptic drugs, new antiepileptic drugs(cannabidiol, fenfluramine)have also shown good antiepileptic effects and are expected to become second-line drugs for the treatment of Dravet syndrome seizures.This article mainly reviews the research progress of unique clinical phenotype, SCN1A gene mutation characteristics and new antiepileptic drugs of Dravet syndrome, in order to deepen clinicians′ understanding of the disease.
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OBJECTIVES@#Hereditary spherocytosis (HS) is the most common hereditary defect of the red cell membrane, mainly characterized by anemia, jaundice, and splenomegaly. Due to the atypical clinical manifestations and negative family history of some patients, as well as the low sensitivity and specificity of traditional laboratory examinations, it is easy for it to escape diagnosis or be misdiagnosed. At present, it has been confirmed that the mutation of ANK1, SPTB, SPTA1, SLC4A1 and EPB42 genes can cause the deletion of their corresponding coding proteins, and thus lead to the defect of erythrocyte membrane. This study aims to analyze the feasibility and clinical application value of HS gene diagnosis.@*METHODS@#Data of 26 patients from Hunan, China with HS admitted to the Department of Hematology, Second Xiangya Hospital of Central South University from January 2018 to September 2021 were retrospectively collected, and their clinical manifestations and results of laboratory examinations were analyzed. Next-generation sequencing (NGS) combined with Sanger sequencing were applied. The mutation of HS pathogenic gene and the variation of uridine diphosphate-glucuronosyl transferase 1 family polypeptide A1 (UGT1A1), a key enzyme in the regulation of bilirubin metabolism, were detected. The results of pathogenic gene variations were interpreted pathogenic gene variations in accordance with the Standards and guidelines for the interpretation of sequence variants published by the American College of Medical Genetics and Genomics (ACMG). The clinical characteristics of patients with different gene variants were analyzed, and the clinical diagnosis and genetic diagnosis were compared.@*RESULTS@#Among the 26 patients with HS, there were 23 cases of anemia, 25 cases of jaundice, 24 cases of splenomegaly, and 14 cases of cholelithiasis. There were 16 cases with family history and 10 cases without family history. The results of HS mutation test were positive in 25 cases and negative in 1 case. A total of 18 heterozygous mutations of HS pathogenic genes were detected in 19 families, among which 14 were pathogenic, 1 was likely pathogenic and 3 were of unknown significance. SPTB mutations (12) and ANK1 mutations (4) were the most common. The main variation types were nonsense mutation (9). There were no significant differences in peripheral blood cell parameters and hemolysis indicators between the SPTB mutant group and the ANK1 mutant group (all P>0.05). The rate of splenectomy in ANK1 mutation group was higher than that in SPTB mutation group, and the difference was statistically significant (χ2=6.970, P=0.014). There were no significant differences in peripheral blood cell parameters and hemolysis indicators among different mutation types (nonsense mutation, frameshift mutation, splice site mutation and missense mutation) (all P>0.05). Among the 18 clinically confirmedpatients, there were 17 cases whose diagnosis is consistent with the genetic diagnosis. Eight patients were clinically suspected, and all of them were confirmed by detection of HS gene mutation. Twenty-four patients with HS underwent UGT1A1 mutation detection, among which 5 patients carried UGT1A1 mutation resulting in a decrease in enzyme activity, and 19 patients had normal enzyme activity. The level of total bilirubin (TBIL) in the group with reduced enzyme activity was higher than that in the group with normal enzyme activity, and the difference was statistically significant (U=22, P=0.038).@*CONCLUSIONS@#Most patients with HS have anemia, jaundice and splenomegaly, often accompanied by cholelithiasis. SPTB and ANK1 mutations are the most common mutations in HS pathogenic genes among patients in Hunan, China, and there was no significant correlation between genotype and clinical phenotype. Genetic diagnosis is highly consistent with clinical diagnosis. The decrease of UGT1A1 enzyme activity can lead to the aggravation of jaundice in HS patients. Clinical combined gene diagnosis is beneficial for the rapid and precision diagnosis of HS. The detection of UGT1A1 enzyme activity related gene variation plays an important role in evaluation of HS jaundice.
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Humains , Codon non-sens , Hémolyse , Études rétrospectives , Splénomégalie , BilirubineRésumé
Objective:To investigate the clinical phenotype and prognosis among different genotypes of progressive familial intrahepatic cholestasis(PFIC) by cases analysis.Methods:The PFIC cases diagnosed at Beijing Children′s Hospital from 2015 to 2022 were collected, and the clinical phenotypic characteristics, treatment and prognosis were compared and analyzed.Results:A total of 628 cases of cholestatic liver disease were diagnosed, and 26 cases of PFIC were found, accounting for 4.1%.The number of PFIC 2 were the most, 14(53.8%)cases; three(11.5%) cases were PFIC 1; five(19.2%)cases were PFIC 3; while two(7.7%) cases were PFIC 4 and PFIC 6, respectively, and there was no case of PFIC 5.Type 1, 2, 4, and 6 had early onset ages(2 days to 21 months), while type 3 had a wide range of onset ages(8 to 145 months). The symptoms included jaundice(96.2%), pruritus(42.3%), and mucosal bleeding(15.4%). All three cases of type 1 had extrahepatic manifestations of diarrhea and malnutrition.Two cases of type 3 were found to have end-stage liver disease.Cases of PFIC 3 had increased serum γ-glutamyltransferase(97.2-439.5 U/L), while those of other types were normal.The bile acids were all increased(10.1-599.6 μmol/L). Abdominal ultrasound mainly showed liver enlargement(80.8%)and enhanced echogenicity of liver parenchyma(73.1%), enlargement of the spleen(61.5%). Ultrasound liver elastography ranged from 6.3 kPa to 23.1 kPa, there were 21(80.8%) cases ≥9 kPa.Among 26 cases, one case was lost to follow-up, and 11 cases were effective by oral medication alone.Fourteen children were still suffering from relapse or progress after drug treatment: four cases received liver transplantation (three cases had a good prognosis and one case died), two cases received biliary drainage, six cases were still taking drugs orally, and two cases died without active intervention in disease progress.Conclusion:Type 2 is the most common type in PFIC.The onset of most cases is in infancy.Jaundice, pruritus and hepatosplenomegaly are common clinical manifestations, and extrahepatic manifestations can be seen in type 1 cases.Type 3 cases can start with end-stage liver disease.Bile acid of all cases are increased.Except for type 3, the serum γ-glutamyltransferase of cases are normal.Oral medication has certain effects on some cases, but more than half progress, and some need biliary diversion or liver transplantation.
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Objective:To summarize the clinical and genetic characteristics of children with epilepsy associated with SCN2A gene variations. Methods:A retrospective study was performed. Eleven children with epilepsy admitted to Department of Pediatric Neurology, Linyi People's Hospital from January 2017 to December 2022 were included; all of them had pathogenic SCN2A gene mutation. Genetic results and clinical data as epileptic seizure type/frequency, intelligence and motor development of these 11 children were collected. Epilepsy-related variations and pathogenesis of SCN2A gene were analyzed, and their correlations with clinical phenotypes in these children were analyzed. Results:Among the 11 patients, 6 had self-limited epilepsy (4 with variation in the intracellular domain and 2 in the transmembrane domain), 1 had febrile convulsion accompanied by childhood absent epilepsy (with variation in the intracellular domain), and 4 had developmental epileptic encephalopathy (2 with variation in the extracellular domain and 2 with variation in the transmembrane domain). SCN2A gene was missense mutation in these 11 children, and the mutation site in 6 children was not reported before. Various forms of video EEG discharge were noted, and 1 child with self-limited epilepsy showed transient multifocal epileptic discharge during frequent seizures. Oxcarbazepine and topiramate were effective for self-limiting epilepsy, and lamotrigine was effective in 1 child with late-onset epileptic encephalopathy. Eleven patients were followed up for (66±32) months; the age ranged from 8 months to 11 years and 6 months at the last follow-up; 10 patients had seizure remission and 1 had uncontrolled seizure. Conclusions:Besides self-limited epilepsy and developmental epileptic encephalopathy, SCN2A gene mutations are also associated with febrile convulsion and childhood absent epilepsy. Phenotypic differences are highly correlated with mutation locations; developmental epileptic encephalopathy associated variants are mostly located in extracellular domains, while self-limited epileptic variants are mostly located in intracellular domains.
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OBJECTIVES@#To investigate the genotypes of the pathogenic gene COL4A5 and the characteristics of clinical phenotypes in children with Alport syndrome (AS).@*METHODS@#A retrospective analysis was performed for the genetic testing results and clinical data of 19 AS children with COL4A5 gene mutations.@*RESULTS@#Among the 19 children with AS caused by COL4A5 gene mutations, 1 (5%) carried a new mutation of the COL4A5 gene, i.e., c.3372A>G(p.P1124=) and presented with AS coexisting with IgA vasculitis nephritis; 3 children (16%) had large fragment deletion of the COL4A5 gene, among whom 2 children (case 7 had a new mutation site of loss51-53) had gross hematuria and albuminuria at the onset, and 1 child (case 13 had a new mutation site of loss3-53) only had microscopic hematuria, while the other 15 children (79%) had common clinical phenotypes of AS, among whom 7 carried new mutations of the COL4A5 gene. Among all 19 children, 3 children (16%) who carried COL4A5 gene mutations also had COL4A4 gene mutations, and 1 child (5%) had COL4A3 gene mutations. Among these children with double gene mutations, 2 had gross hematuria and proteinuria at the onset.@*CONCLUSIONS@#This study expands the genotype and phenotype spectrums of the pathogenic gene COL4A5 for AS. Children with large fragment deletion of the COL4A5 gene or double gene mutations of COL4A5 with COL4A3 or COL4A4 tend to have more serious clinical manifestations.
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Humains , Néphropathie familiale avec surdité/anatomopathologie , Hématurie/complications , Études rétrospectives , Collagène de type IV/génétique , Génotype , MutationRésumé
Objective:To analyze the clinical phenotype of adult patients with epidemic encephalitis B (encephalitis B) in Ningxia Hui Autonomous Region, and to explore the influence of related factors of the development of encephalitis B.Methods:The medical records of confirmed patients with encephalitis B admitted to the General Hospital of Ningxia Medical University from August to November 2018 were collected, and the general data of patients and the results of laboratory indexes such as blood routine examination and cerebrospinal fluid routine examination were analyzed. Logistic regression analysis and survival curve were used to evaluate the risk factors of the development of encephalitis B.Results:Totally 97 patients with encephalitis B were included, 32 of them died, with a case fatality rate of 32.99%. There were 63 males and 34 females, and the age of onset was (59.13 ± 14.70) years old. There were statistically significant differences in case distribution rate between different sexes and ages (χ 2 = 97.00, 291.00, P < 0.001). The most common clinical type was extremely severe (43 cases), followed by mild (27 cases), severe (15 cases) and ordinary (12 cases). The results of laboratory tests showed that the number of neutrophils, lymphocytes and monocytes in the blood of patients increased; and the white blood cells number in cerebrospinal fluid increased significantly, while neutrophils ratio increased slightly. There were significant differences in cerebrospinal fluid glucose level and neutrophil ratio among patients with different clinical types of encephalitis B ( H = 4.21, 2.74, P < 0.05). There were statistically significant differences in death, hypertension, cerebrovascular diseases, and pulmonary infection among patients with different clinical types of encephalitis B (χ 2 = 34.22, 16.97, 9.91, 15.59, P < 0.05). Logistic regression analysis showed that hypertension [ OR (95% CI) = 5.544 (1.450-21.191)] and pulmonary infection [ OR (95% CI) = 6.490 (1.887-22.325)] were risk factors for the development of encephalitis B patients ( P = 0.012, 0.003). Pulmonary infection was the influencing factor for the death of encephalitis B patients (χ 2 = 18.88, P < 0.001). The survival curve showed that the survival status of encephalitis B patients with cerebrovascular disease and pulmonary infection was significantly worse than that of patients without comorbidity or complications (χ 2 = 6.45, 20.33 , P < 0.05). Conclusions:The majority of encephalitis B patients in this outbreak are the elderly people, and the patient's nervous system has inflammatory reaction. Complicated pulmonary infection is an important factor for the aggravation and death of encephalitis B patients.
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Objective:The clinical phenotypes and pathogenicity of isolated cone-rod dystrophy (CORD) caused by two novel complex heterozygous variants of the CEP290 gene were analyzed using high-resolution multi-mode imaging and gene detection techniques. Methods:A retrospective study. Two patients and two family members from a CORD family who were diagnosed by genetic testing at Henan Provincial People's Hospital in December 2021 were included in the study. All subjects underwent best-corrected visual acuity (BCVA), color fundus photography, autofluorescence, swept-source optical coherence tomography (SS-OCT), adaptive optics fundus imaging, static threshold field, full field and multiple electroretinogram (ERG) examination, as well as other systemic examinations throughout the body. The peripheral venous blood of the subjects was collected, and the whole genome DNA was extracted. DNA sequencing was performed using the Inherited Retinal Disease Kit PS400, and Sanger verification and pedigree co-segregation analysis were performed on the suspected pathogenic mutation sites. Validation was performed by Sanger sequencing, pathogenicity analysis was performed in accordance with the American College of Medical Genetics and Genomics (ACMG) guidelines. Conservation of variation among different species was analyzed by GERP++, Clustal Omega and Weblogo.Results:Both patients were male, and their ages were 21 and 29 years old, respectively. The right eye and left eye about BCVAs were 0.7, 0.4 and 0.3, 0.4, respectively. The full field and multiple electroretinogram ERG showed a decreased function of cones and rods, especially cones. SS-OCT showed thinning of the outer nuclear layer of macular, and attenuation of ellipsoid zone reflectivity in B-scan. Adaptive optics fundus imaging examination showed that the arrangement of cone cells in the fovea of the fovea was disordered and the density decreased, and the retinal pigment epithelial cells were seen through the atrophy of cone cells in some areas at 10°visual angle. No obvious abnormality was found in other systemic examinations of the whole body. Genetic testing showed that 2 novel compound heterozygous variants c.950T >A (p.Leu317*) (M1) and c.4144_4149del (p.Tyr1382_Glu1383del) (M2) in CEP290 were found in two patients. The first variant was predicted to be harmful in MutationTaster and CADD. GERP++ showed highly conserved among different species. The pathogenicity of the variant was suspected to be likely pathogenic according to ACMG guidelines. The pathogenicity of the second variant was uncertain significance. The parents of the proband had no similar ocular abnormalities. Verified by Sanger sequencing, it was consistent with co-separation in the family. Conclusions:Patients with pure CORD caused by CEP290 gene mutation still retain better vision when the cone structure is abnormal, the density is decreased, and the function of cone and rod cells is decreased. CEP290 M1 and M2 are newly discovered nonsense mutations and newly discovered deletion mutations, which expanded the causative gene spectrum of pure CORD.
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Objective:To identify 3 the disease-causing genes and mutations of Leber congenital amaurosis (LCA), and to study the correlation of phenotype and genotype.Methods:A retrospective study. Four LCA patients and seven family members who were diagnosed by eye examination in Ning Xia Eye Hospital of People's Hospital of Ningxia Hui Autonomous Region from January to December 2021 were included in the study. Four patients were from 3 unrelated families. Detailed collection of medical history and family history were received. Related ophthalmologic examination were collected and genomic DNA was extracted from peripheral blood. Whole-exome sequencing method was used for genetic diagnosis. The identified variant was confirmed with Sanger sequencing. Potential pathogenic mutation was analyzed using software and conserved domain analysis and performed co-separated analysis between the family member and the proband.Results:Of the 4 patients, 1 patient was males and 3 patients were females; the age was from 4 to 18 years. Nystagmus were seen in 3 cases, finger pressing eyes and night blindness was seen in 1 cases; electroretinogram showed 4 cases of extinction or near extinction. The foveal reflection was visible in all eyes, and there was no obvious abnormality in the peripheral retina. One eye had strong reflection signal with raised ellipsoid in macular area; two eyes had weak reflection signal faintly visible between retinal layers; 1 eye had increased blood vessel branches, peripheral retinal non-perfusion area with capillary leakage; annular strong autofluorescence in macular area 4 eyes. No obvious abnormality was found in the phenotypes of family members. Genetic testing showed that the proband of pedigree 1 (Ⅱ-1) was found a homozygous missense mutation in c.640A>T (p.C214S) (M1) of PRPH2 gene. The proband of pedigree 2 (Ⅱ-2) was found compound heterozygous mutation in c.1256G>A(p.R419Q) (M2) and c.1A>C (p.M1L) (M3) of TULP1 gene. The proband 3 (Ⅱ-1) and her sister (Ⅱ-2) were both found compound heterozygous mutation in c.1943T>C (p.L648P) (M4) and c.380C>T (p.P127L) (M5) of GUCY2D gene. The parents and sister (Ⅱ-1) of the proband in family 2 and the parents of the proband in family 3 were all carriers of the corresponding heterozygous variant. M1, M3, M4, M5 were novel mutations and unreported. The genotype and disease phenotype were co-segregated within the family. According to the analysis of pedigree and genetic testing results, all 3 families were autosomal recessive inheritance. The amino acid conservation analysis found that M1, M2, M3, M4, and M5 were highly conserved among species. The results of bioinformatics analysis were all pathogenic variants. Conclusions:PRPH2 gene M1, TULP1 gene M3, and GUCY2D gene M4, M5 were novel mutations and not been reported in the literature and database. This research expanded the gene mutation spectrum of LCA. The patients with LCA have available characterristics, including onset age, varying ocular fundus and severe visual impairment.
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Primary ciliary dyskinesia (PCD) is a hereditary disease characterized by airway mucociliary clearance dysfunction. The estimated prevalence of PCD is 1꞉10 000 to 1꞉20 000. The main respiratory manifestations in children are cough, expectoration, chronic rhinitis, sinusitis, and chronic otitis media, while the most common symptoms in adults are chronic sinusitis, bronchiectasis, and infertility. About 50% of patients with certain PCD-related gene variants are combined with situs inversus, and the incidence of congenital heart disease is also high. The pathogenesis behind PCD is that gene variants cause structural or functional disorders of respiratory cilia and motile cilia of other organs, leading to a series of heterogeneous clinical manifestations, which makes it difficult to identify and diagnose PCD. Combining different disease screening tools and understanding the relationship between genotypes and phenotypes may facilitate early diagnosis and treatment for PCD.
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Humains , Maladie chronique , Cils vibratiles/anatomopathologie , Syndrome de Kartagener/génétique , Phénotype , SinusiteRésumé
Clinical data of a child with congenital myopathy caused by the SPEG gene mutation diagnosed in the Children′s Hospital of Nanjing Medical University in March 2020 were retrospectively analyzed, and the relevant literature was reviewed.A 13-year-old female child with lagged motor development since childhood, weakness of both lower extremities for 10 years, and slow progression of disease.Physical examinations showed gait swinging, mild hypertrophy of gastrocnemius, positive Gower sign, grade Ⅴ distal muscle strength of both lower extremities, and grade Ⅳ proximal muscle strength.The electromyography showed myogenic damage changes.Her 11-year-old sister presented similar symptoms of muscle weakness.Gene sequencing revealed compound heterozygous mutations in the SPEG gene, with the newly reported mutation sites at c. 3715+ 4C>T and c. 3588delC, which had not been reported at home and abroad.This study for the first time reported a case of congenital myopathy caused by the SPEG gene mutation in China, which differed from previous cases accompanied cardiomyopathy.This case report expanded the mutation spectrum of the SPEG gene.
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Multiple sclerosis ( MS) is an immune-mediated chro¬nic inflammatory disease of the central nervous system (CNS) , which is regulated by multiple pathophysiological mechanisms.There are four clinical phenotypes of MS, including relapsing-re- mitting MS ( RRMS) , primary progressive MS ( PPMS) , sec- ondary-pmgressive MS ( SPMS) , and progressive relapsing MS ( PRMS) , among which RRMS is the main type.'Hie pathogen¬esis of MS is not clear and it could not he cured, so long-term drug treatment is needed for the MS patients.Nowadays, animal models play an important role in the preclinical research of MS drugs.'Hie MS animal models are mainly divided into experi¬mental autoimmune encephalomyelitis (EAE) model, toxin in¬ duced demyelination model, and vims induced demyelination model, among which EAE model is most widely used.'Hie three types of MS animal models demonstrate specific characteristics due to the different induction methods and animal species, and they correspond to specific clinical types of MS.According to the different clinical types of MS, the use of appropriate animal models for drug research and development will help us develop more targeted and potential therapeutic dnrgs, making it possible to cure MS.
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Objective:To investigate the clinical and genetic features of children with Arts syndrome.Methods:The clinical features of a child with Arts syndrome diagnosed in Department of Neurology, Children′s Hospital of Nanjing Medical University were retrospectively analyzed.Relevant literatures about Arts syndromes were reviewed as well.Results:It was a 17-month-old boy with initial symptoms of hearing loss after birth, delayed motor development and early-onset hypotonia.At the age of 15 months old, the boy had respiratory failure due to pneumonia.Electromyographic suggested multiple peripheral neurogenic lesions.Visual evoked potentials were normal.Gene sequencing of PRPS1 of the boy revealed a novel hemizygous missense c. 421C>T (p.P141S) hemizygote missense mutation, and therefore, the boy was diagnosed as Arts syndrome.Motor development improved after rehabilitation treatment.Through literature review, 14 children with Arts syndrome, including 4 genotypes of missense mutations were reviewed in 4 English-published literatures.These cases had similar manifestations with the case reported in this study.Conclusions:Arts syndrome is a rare X-linked recessive inheritant disorder caused by PRPS1 mutations with complex clinical phenotypes.The novel missense mutation c. 421C>T found in this study expands the PRPS1 gene mutation profile.
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Objective:To investigate the clinical characteristics of two Han families with familial vitreous amyloidosis (FVA) and the gene mutation.Methods:A pedigree investigation was performed.Two Han Chinese families with FVA treated in Xiangya Hospital of Central South University from January 2015 to December 2018 were collected.General examination and ophthalmic examination were performed among 112 members of the two families.Peripheral blood samples were collected from 32 family members (15 patients in MZ001 pedigree, 7 patients in MZ002 pedigree, and 5 persons with normal clinical phenotype from each pedigree) for DNA extraction, polymerase chain reaction (PCR) amplification, transthyretin ( TTR) gene screening and sequencing.Vitreous biopsy following three-channel 23-gauge pars plana vitrectomy was performed on the two probands in the two families.Vitreous specimens were sent for pathological examination.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Xiangya Hospital of Central South University (No.201412463), and written informed consent was obtained from all subjects before any medical examination. Results:In MZ001, there were 15 cases of the 63 members presented bilateral vitreous opacity at an average age of (43.6±5.8) years.No lesion was found in nervous system, cardiovascular system, kidney or liver in general inspection.The vitreous of the proband (Ⅲ13) was so sticky that could not be totally removed during vitrectomy.The vitreous specimen showed positive Congo red staining.Ⅲ13 had elevated intraocular pressure after vitrectomy and was diagnosed as open-angle glaucoma.Gene sequencing revealed Gly83Arg mutation in the exon 3 of TTR gene.In MZ002, 7 cases of 49 members had bilateral vitreous opacity at an average age of (50.4±5.5) years, among which, 3 cases appeared symptoms of limb numbness and decreased muscle strength.The vitreous body of the proband (Ⅱ11) in MZ002 pedigree was looser and easier to remove during vitrectomy than that of Ⅲ13 in MZ001 pedigree.Vitreous specimen of Ⅱ11 was positive with Congo red staining.Gene sequencing revealed an Ala36Pro variant in the exon 3 of TTR gene. Conclusions:Gly83Arg or Ala36Pro mutation of TTR gene can cause FVA.Different mutations can lead to different clinical phenotypes such as age of onset, clinical symptoms and complications of other systems.
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Objective:To investigate the relationship between double mutations of myosin heavy chain gene (MYH6) p.Gly743Arg and p.Glu1389Lys and the cardiac phenotype.Methods:Patients carrying double mutations in the MYH6 gene p.Gly743Arg and p.Glu1389Lys were screened from 52 unrelated left ventricular hypertrophy (LVH) who were admitted to the Second Hospital of Chongqing Medical University from 2015 to 2020, and the genetic testing of peripheral blood of patients by second-generation whole-exome sequencing assay technology and genomic DNA of their family members Sanger sequencing was performed to validate the genomic DNA of the family members. The cardiac phenotype was evaluated by electrocardiogram, coronary computed tomography angiography (CTA), echocardiography, and cardiac magnetic resonance imaging (MRI) as adjuncts.Results:All whole-exome gene were detected in 52 unrelated patients with LVH, of which 1 patient (1.9%) had double mutations in MYH6 gene p.Gly743Arg and p.Glu1389Lys (proband). Two members of the maternal line of this patient carried p.Glu1389Lys mutation, but there was no obvious clinical phenotype. Two members of the paternal line carried p.Gly743Arg mutation and had obvious clinical phenotype of bradycardia, but there was no LVH. The male proband, aged 21 years old, presented with LVH and sinus bradycardia but no coronary artery stenosis on CTA before treatment, MRI showed that the left ventricular end diastolic diameter was 58 mm. After treatment with angiotensin receptor-enkephalinase inhibitor (ARNI), electrocardiogram showed that the heart rate increased significantly (from 43 bpm to 72 bpm). Echocardiography showed that the left ventricular end diastolic diameter decreased significantly (from 60 mm to 49 mm).Conclusions:The p.Glu1389Lys mutation of the MYH6 gene may not manifest the phenotype of heart disease. MYH6 gene p.Gly743Arg mutation may be manifested asymptomatic sinus bradycardia, but there is no LVH phenotype. The cardiac disease phenotype caused by the double mutations of p.Gly743Arg and p.Glu1389Lys in the MYH6 gene is more obvious. Asymptomatic LVH and sinus bradycardia can appear in adolescence, but the LVH phenotype can be reversed in a short period of time after ARNI treatment.
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OBJECTIVE@#To explore the difference in phenotype recognition of PsA patients in two clinical scenarios, physical examination with and without ultrasound assessment.@*METHODS@#PsA patients who visited the rheumatology and clinical immunology department of Peking University First Hospital between January 2010 and October 2020, with complete data of clinical and ultrasound assessment were enrolled. The phenotypes were first identified based on physical examination only, and then combined with enthesitis and dactylitis shown on power doppler and gray-scale ultrasound. The phenotype groupings without and with ultrasound assessment were presented with Wayne diagram. The distributions of different clinical phenotypes were compared by using χ2 test or Fisher's exact test. The differences of clinical phenotypes with and without ultrasound assessment were compared by using Wilcoxon signed rank test.@*RESULTS@#A total of 227 patients with PsA were enrolled with one or more clinical domains. Physical examination revealed that psoriasis was in 209 (92.1%, 209/227) patients, nail involvement in 98 (43.2%, 98/227) patients, peripheral arthritis in 219 (96.5%, 219/227) patients, axial involvement in 25 (11.0%, 25/227) patients, dactylitis in 80 (35.2%, 80/227) patients, and enthesitis in 18 (7.9%, 18/227) patients. Besides 18 patients with clinical enthesitis, ultrasound scan revealed acute enthesitis in 80 patients, with hypoechogenicity (55 cases), tendon thickening (62 cases), and presence of Doppler signals (48 cases). Similarly, dactylitis on ultrasound was found in 18 patients besides those patients with clinical dactylitis. Compared with the phenotypes recognized based on physical examination only, the additional ultrasound assessment revealed that the most common phenotypes, peripheral arthritis was significantly less frequently recognized (49.8% vs. 27.8%, P < 0.001), however on the other hand, the proportion of the patients with peripheral arthritis and enthesitis was significantly increased (4.4% vs. 18.1%, P < 0.001). The phenotype of peripheral arthritis combined with enthesitis, and dactylitis was also dramatically increased (1.8% vs. 17.6%, P < 0.001).@*CONCLUSION@#Ultrasound is a useful tool to identify enthesitis and dactylitis. With the aid of ultrasound assessment, rheumatologists can better identify the lesions of PsA, accurately identify the phenotypes, and further guide the subsequent treatment.
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Humains , Arthrite psoriasique/imagerie diagnostique , PhénotypeRésumé
Juvenile dermatomyositis (JDM) is an autoimmune disease manifesting as proximal muscle weakness and skin rash and can involve multiple systems and visceral organs. Myositis-specific autoantibodies (MSAs) are highly associated with various complications and prognosis in JDM. Patients with anti-Mi-2 antibodies tend to have good prognosis and typical clinical symptoms. Patients with anti-MDA5 antibodies often have diffuse interstitial lung disease and skin ulcer, with mild symptoms of myositis. Patients with anti-NXP2 antibodies often have calcinosis, and such antibodies are associated with gastrointestinal bleeding and perforation. Patients with anti-TIF1-γ antibodies have diffuse and refractory skin lesions. Anti-SAE antibodies are rarely detected in children, with few reports of such cases. This article reviews the features of clinical phenotypes in JDM children with these five types of MSAs, so as to provide a basis for the clinical treatment and follow-up management of children with JDM.
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Humains , Autoanticorps , Dermatomyosite , Pneumopathies interstitielles/étiologie , Myosite , PronosticRésumé
Primary age-related tauopathy (PART) is a type of pathological change characterized by the deposition of tau protein in the brain confined to the entorhinal cortex and hippocampus (Braak stage 0-Ⅳ), with no or little amyloid-β protein (Aβ) deposition (Thal Aβ stage 0-2). In recent years, PART has received lots of attention, but its relationship with Alzheimer's disease (AD) remains controversial. Therefore, strengthening the understanding of PART among clinicians and relevant researchers is of great value in interpretation of the relationship between brain aging and AD as well as other cognitive impairment diseases.
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Objective@#To explore the relationship between different mutation characteristics and clinical phenotype of children with Dravet syndrome (DS) with SCN1A gene mutation, and to summarize the drug efficacy.@*Methods@#The clinical data of children diagnosed as DS from the Department of Pediatrics Neurology, the Third Affi-liated Hospital of Zhengzhou University from January 2014 to May 2018 were collected.The peripheral blood DNA of the children was detected by adopting next generation sequencing for epilepsy-related gene-panel, while the parents′ were screened by using Sanger sequencing for family verification.Multiple ligation-dependent probe amplification technology was used to detect large fragment variation of SCN1A gene if the mutations of the children were negative.The Gesell scale and cavity Wechsler intelligence scale for children(C-WISC) were used to evaluate the intelligence of children.@*Results@#A total of 50 cases of DS were collected, 38 cases of them were positive for SCN1A mutation, and the mutation rate was 76.0%(38/50 cases), of which, the missense mutation[50.0%(19/38 cases)] and frameshift mutation[28.9%(11/38 cases)] were dominant.The average onset age of 50 patients was 6 months, of which onset of seizures was triggered by fever(temperature>37.5 ℃) in 68.0%(34/50 cases)of children, the history of seizures in hot baths was found in 60.0%(30/50 cases) of children, status epilepticus was found in 74.0%(37/50 cases), cluster-like episodes was found in 80.0%(40/50 cases), ≥2 seizure types was found in 92.0%(46/50 cases). Mental retarda-tion was found in most of the children, of which 30.0% (15/50 cases) were mild mental retardation, 38.0% (19/50 cases) were moderate mental retardation, 14.0% (7/50 cases)were severe intelligence retardation.Interictal abnormalities of electroencephalogram(EEG) before 1 year old was found in 24.0%(12/50 cases), and the average age of EEG abnormalities was 30.12 months old; the top three drug efficacy rates were 70.0% (28/40 cases) of Topiramate, 48.0% (24/50 cases) of Sodium Valproate, 45.7% (16/35 cases) Clonazepam or Clobazam.The time of onset of myoclonus and atypical absence of the truncation mutation group was earlier than that of the missense mutation group(14.75 months vs.21.20 months; 16.82 months vs.26.00 months), and the difference was statistically significant(P<0.05). The proportion of clustered episodes in the truncation mutation group was higher than that in the missense mutation group [94.7%(18/19 cases)vs.63.2%(12/19 cases)], and the difference was statistically significant (P<0.05). There was no significant correlation between the SCN1A gene mutation (type and position) and age of onset, type of seizure, proportion of convulsion persistence, the mental development or abnormal proportion of EEG and seizure frequency before 1 year old(all P>0.05).@*Conclusions@#The SCN1A gene mutation rate is high in children with DS, and the SCN1A gene mutation characteristics has a certain correlation with DS clinical phenotype.Topiramate is the most effective drug among children with DS.
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More than 150 different human proteins are anchored to the outer leaflet of the plasma membrane via glycosylphosphatidylinositol (GPI). From the synthesis of GPI anchors, binding to proteins to localization on cell membranes, these processes are regulated by a wide range of genes, including PIG genes such as PIGA, PIGB, PIGC, and PGAP genes such as PGAP1, PGAP2, etc.Recently, the number of reports about PIG/PGAP gene related diseases is increasing but rarely reported in China.Now, the inheritance and clinical features, treatment and genotype/phenotype associated with PIG/PGAP gene related diseases, were reviewed.