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More than 100 genes located on the X chromosome have been found to be associated with X-linked intellectual disability (XLID) to date, and NEXMIF is a pathogenic gene for XLID. In addition to intellectual disability, patients with NEXMIF gene mutation can also have other neurological symptoms, such as epilepsy, abnormal behavior, and hypotonia, as well as abnormalities of other systems. Two children with intellectual disability and epilepsy caused by NEXMIF gene mutation were treated in the Department of Pediatrics, Xiangya Hospital, Central South University from March 8, 2017 to June 20, 2020. Patient 1, a 7 years and 8 months old girl, visited our department because of the delayed psychomotor development. Physical examination revealed strabismus (right eye), hyperactivity, and loss of concentration. Intelligence test showed a developmental quotient of 43.6. Electroencephalogram showed abnormal discharge, and cranial imaging appeared normal. Whole exome sequencing revealed a de novo heterozygous mutation, c.2189delC (p.S730Lfs*17) in the NEXMIF gene (NM_001008537). During the follow-up period, the patient developed epileptic seizures, mainly manifested as generalized and absent seizures. She took the medicine of levetiracetam and lamotrigine, and the seizures were under control. Patient 2, a 6-months old boy, visited our department due to developmental regression and seizures. He showed poor reactions to light and sound, and was not able to raise head without aid. Hypotonia was also noticed. The electroencephalogram showed intermittent hyperarrhythmia, and spasms were monitored. He was given topiramate and adrenocorticotrophic hormone (ACTH). Whole exome sequencing detected a de novo c.592C>T (Q198X) mutation in NEXMIF gene. During the follow-up period, the seizures were reduced with vigabatrin. He had no obvious progress in the psychomotor development, and presented strabismus. There were 91 cases reported abroad, 1 case reported in China, and 2 patients were included in this study. A total of 85 variants in NEXMIF gene were found, involving 83 variants reported in PubMed and HGMD, and the 2 new variants presented in our patients. The patients with variants in NEXMIF gene all had mild to severe intellectual disability. Behavioral abnormalities, epilepsy, hypotonia, and other neurological symptoms are frequently presented. The phenotype of male partially overlaps with that of female. Male patients often have more severe intellectual disability, impaired language, and autistic features, while female patients often have refractory epilepsy. Most of the variants reported so far were loss-of-function resulted in the reduced protein expression of NEXMIF. The degree of NEXMIF loss appears to correlate with the severity of the phenotype.
Subject(s)
Child , Female , Humans , Male , Epilepsy/genetics , Intellectual Disability/genetics , Muscle Hypotonia/complications , Mutation , Phenotype , Seizures/genetics , Strabismus/complicationsABSTRACT
Myasthenia gravis (MG) is an autoimmune disease with neuromuscular junction (NMJ) transmission disorder mediated by various antibodies, dependent on cellular immunity, and involved in complement and cytokines. MG is one of the common diseases in pediatric neurology, which is different from adult MG in diagnosis and treatment. However, there is still a lack of accurate and efficient diagnosis and treatment plan for pediatric MG. In recent years, with the development of pathogenesis, targeted diagnosis and treatment of NMJ transmission disorders caused by immune network disorders in immunopathology and pathogenic antibodies is the current main research direction. This article reviews the progress of auxiliary examination and treatment of MG in children.
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Cardio-facio-cutaneous (CFC) syndrome is an extremely rare autosomal dominant genetic disease due to BRAF and other gene mutations. The main characteristics of the patients are craniofacial deformities, cardiac malformations, skin abnormalities, delay of language and motor development, gastrointestinal dysfunction, intellectual disability, and epilepsy. In this case, the child has a typical CFC syndrome face and developmental delay. The gene results of the second-generation sequencing technology showed that there was a mutation site c.1741A>G (p. Asn581Asp) (heterozygous) in exon 14 of the BRAF (NM_004333.5) gene. The mutation was not observed in the child's parents. The above-mentioned mutation may be a de novo mutation. There is no effective therapy for this disease so far.
Subject(s)
Child , Humans , Abnormalities, Multiple , Ectodermal Dysplasia/genetics , Facies , Failure to Thrive , Heart Defects, Congenital/genetics , Mutation , Proto-Oncogene Proteins B-raf/geneticsABSTRACT
Objective According to the clinical and gene mutation characteristics of ACADVL-related very long chain acyl-CoA dehydrogenase deficiency(VLCADD),the types that contribute to the gene mutation of ACADVL were summarized.Methods By analyzing clinical,laboratory and genetic data of 1 case with ACADVL-related very long chain acyl-CoA dehydrogenase deficiency diagnosed from Department of Pediatrics,the Affiliated Hospital of Inner Mongolia Medical University in August 2016,based on the agreement signed by both the litde patient's parents and the hospital,plus the high-throughput sequencing analysis and PCR sequencing test for the 2 generation genes,some presented mutation sites were analyzed and concluded,in addition to taking "ACADVL" as key words to search the databases from CNKI,Wanfang(updated in 2016) as well as PubMed and related documents from On-line Mendal Inheritant databases of Man (OMIM) and HGMD.Results Through physical examination,VLCADD was diagnosed.After being given Levocamitine and the diet likemedium-chain fatty acid food for a week,the metabolism returned to normal.Tracking him for 3 months,his hepatitis obviously rebounded,within the reach of 3 cm under the right rib and 1 cm under the xiphoid.The exome sequencing study (trios) was identified the novel heterozygous mutation according to the statistics below A CAD VL (N M_000018.3) Exon7:c.608 C ＞ T;p.(Pro203 Leu) (heterozygous) and A CAD VL (NM _000018.3) Exon18:c.1748C ＞ T;p.(Ser583Leu) (heterozygous) in ACADVL.Relevant literature reported suggest these two mutations from both the parents are pathogenic genes,which can account for the reason why the boy got ill.However,these two mutations had not been reported in ACADVL-related VLCADD so far.Up to now,73 types of mutations from documents index were related to the VLCADD,but the clinical case included 75 kinds of gene mutations.Conclusions The apparent symptoms of the boy with the gene mutation were reflected in abnormal heart rates,hepatomegaly and hypoglycemia.VLCADD was diagnosed through genetic testing,and systematic treatment can partly control the development of the disease.In conclusion,the findings (exon 7 and 18) show that according to the genetic tests,disease-causing genes from both parents are new mutations of ACADVL and they are pathogenic.
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Interleukin-33 is regarded as the orphan receptor ST2 that belongs to the cytokine family of interleukin-1 in 2005. IL-33 is found to play a potentially pathogenic roles in the autoimmune disease, allergic disease, vascular disease, inflammatory disease and it might be a useful sera marker for the diagnosis and prognosis in related diseases. Here we make a review on the relationship between IL-33 and autoimmune disease in recent years.
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Adhesion molecules (AM) are a class of molecules that can mediate cell-to-cell and cell-to-matrix interaction. They participate in the cellular recognition, signal transduction, cell proliferation and differentiation, cell stretching and movement through ligand-to-receptor interaction. AM are the molecular basis of immune response, inflammation, blood coagulation, tumor metastasis, wound healing and a series of physiological and pathological processes. Kawasaki disease (KD) is an acute systemic small vasculitis syndrome, mainly affecting coronary artery. KD is the main cause for acquired heart disease in children. To study the relationship between AM and pathogenesis of KD is important in the understanding of KD pathogenesis, prevention and treatment of coronary artery lesions complicated with KD. This review focused on the relationship between AM and pathogenesis of KD.
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Anti-endothelial cell antibodies (AECA) are heterogeneous autoimmune antibodies, which target at a group of antigens expressed in endothelial cells. In 1971, AECA was reported by Lindquist and Osterland for the first time. Since then, an increasing number of researches have showed that AECA exists and plays potential pathogenic role in the immune or inlfammation-related diseases, especially in systemic vasculitis. AECA may be a useful sera marker for the diagnosis and prognosis judgment of related autoimmune diseases. In this review, we summarize the recent progress on the relationship between AECA and systemic vasculitis.
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Objective To explore the effect and mechanism of fluvastatin preventing and curing restenosis. Methods 48 rabbits were randomly divided into 3 groups. In control group, rabbits were given basic food. In balloon injury group, rabbits were given basic food and balloon injury of general artery on right neck. In fluvastatin balloon group, rabbits were given basic food,ballon injury of general artery and 10mg?kg -1 ?d -1 fluvastatin. The expression of MMP-9 and TIMP-2 of mRNA was detected at 3, 7, 14 and 30 days after injury respectively by method of in site hybridization. Results There was little expression of MMP-9 and TIMP-2 mRNA in control group, and the expression of MMP-9 and TIMP-2 mRNA in middle membrane of blood vessels began at 3 days after blood injury, and reached maximum at 7 days after injury. There was a little expression of MMP-9 and TIMP mRNA in inner membrane of blood vessels at 14 and 30 days after injury, and MMP-9 expression significantly decreased after the fluvastatin interference(P
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Objective To explore the level of soluble intercellular adhension molecule-1 (sICAM-1) in the patients with acute ischemic cerebrovascular disease (AICVD) and its clinical significance. Methods The level of sICAM-1 was determined by double-antibody enzyme linked immunosorbent in 67 patients with AICVD and 45 patients being susceptible to AICVD. 40 healthy subjects served as normal control group. Results The level of sICAM-1 in the patients with AICVD was significantly higher than that in the patients being susceptible to AICVD (P
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Objective:To approach the significance of serum C-Reactive protein(CRP) and matrix metalloproteinases-9(MMP-9) levels in the diagnosis unstable angina(UA) and its forecasting of prognosis .Methods:The serum CRP levels of 38 cases of UA,36 cases of stable angina(SA) and 35 cases of normal controllers was measured by immunoturbidimetric method.And meanwhile,the serum MMP-9 levels of the above-mentioned three groups was measured by enzyme linked immunosorbent assay(ELISA).Results:When the groups were hospitalized,the CRP levels of the UA group(5.85?2.23 mg/L)was evidently higher than that of the SA group(2.54?1.07 mg/L)and the normal control group(1.21?1.02 mg/L)( P
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Objective To study the expression and distribution of protein STAT3 in the retina after optic nerve transection. Methods Immunocytochemistry, Western blot and computer image analysis techniques were used. Results After optic nerve transection, STAT3 levels in the retina was highly up-regulated, the peak of which appeared at day 1 postaxotomy, then decreased gradually to the normal level 5 days later. More translocations of STAT3 to the nucleus were seen.Conclusion JAK-STAT signal transduction pathway was involved in the pathological processes in the retinal after transection of the optic nerve.