X-linked Charcot-Marie-Tooth disease after SARS-CoV-2 vaccination mimicked stroke-like episodes: A case report

BACKGROUND Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) vaccinations have been administered worldwide, with occasional reports of associated neurological complications. Specifically, the impact of vaccinations on individuals with Xlinked Charcot-Marie-Tooth disease type 1(CMTX1) is unclear. Patients with CMTX1 can have stroke-like episodes with posterior reversible encephalopathy syndrome on magnetic resonance imaging(MRI), although this is rare.CASE SUMMARY A 39-year-old man was admitted with episodic aphasia and dysphagia for 2 d. He received SARS-CoV-2 vaccination 39 d before admission. Physical examination showed pes cavus and reduced tendon reflexes. Brain MRI showed bilateral, symmetrical, restricted diffusion with T2 hyperintensities in the cerebral hemispheres. Nerve conduction studies revealed peripheral nerve damage. He was diagnosed with Charcot-Marie-Tooth disease, and a hemizygous mutation in the GJB1 gene on the X chromosome, known to be pathogenic for CMTX1, was identified. Initially, we suspected transient ischemic attack or demyelinating leukoencephalopathy. We initiated treatment with antithrombotic therapy and immunotherapy. At 1.5 mo after discharge, brain MRI showed complete resolution of lesions, with no recurrence.CONCLUSION SARS-CoV-2 vaccination could be a predisposing factor for CMTX1 and trigger a sudden presentation.

Mutation Analysis of Gap Junction Protein Beta 1 and Genotype-Phenotype Correlation in X-linked Charcot-Marie- Tooth Disease in Chinese Patients

Background： Among patients with Charcot-Marie-Tooth disease （CMT）, the X-linked variant （CMTX） caused by gap junction protein beta 1 （GJB1） gene mutation is the second most frequent type, accounting for approximately 90% of all CMTX. More than 400 mutations have been identified in the GJB1 gene that encodes connexin 32 （CX32）. CX32 is thought to form gap junctions that promote the diffusion pathway between cells. GJB1 mutations interfere with the formation of the functional channel and impair the maintenance of peripheral myelin, and novel mutations are continually discovered. Methods： We included 79 unrelated patients clinically diagnosed with CMT at the Department of Neurology of the Chinese People＇s Liberation Army General Hospital from December 20, 2012, to December 31, 2015. Clinical examination, nerve conduction studies, and molecular and bioinformatics analyses were performed to identify patients with CMTX 1. Results： Nine GJBI mutations （c.283G〉A, c.77C〉T, c.643C〉T, c.515C〉T, c.191G〉A, c.610C〉T, c.490C〉T, c.491G〉A, and c.44G〉A） were discovered in nine patients. Median motor nerve conduction velocities of all nine patients were 〈 38 m/s, resembling CMT Type 1. Three novel mutations, c.643C〉T, c.191G〉A, and c.610C〉T, were revealed and bioinformatics analyses indicated high pathogenicity. Conclusions： The three novel missense mutations within the GJB1 gene broaden the mutational diversity ofCMT1X. Molecular analysis of family members and bioinformatics analyses of the afflicted patients confirmed the pathogenicity of these mutations.

色素失禁症11例临床特征分析

【目的】探讨色素失禁症患儿临床特征，提高对该病的认识。【方法】对本院2004年1月至2013年12月收治的色素失禁症11例患儿临床特点进行分析。【结果】11例患儿中10例为女性，1例男性，2例为双胞胎早产儿。11例均有皮肤受累，神经系统受累发生惊厥2例，眼部受累2例。6例外周血嗜酸性粒细胞数比例明显升高，4例行皮肤活检，病理结果疱内有大量嗜酸性细胞支持诊断，1例核转录因子κB必需调节器（NEMO）基因缺失。【结论】色素失禁症是一种少见的 X连锁的显性遗传病，新生儿期皮肤损害显著，可累及多系统，眼部及神经系统病变严重，应得到早期诊断；皮肤病理和染色体的基因分析是确诊方法，应对患儿进行定期随访。

Serum Biomarkers for Early Diagnosis of Chinese X-CGD Children:Case Reports and a Literature Review

Since X-linked chronic granulomatosis disease(X-CGD)exhibits no specific clinical symptoms at an early stage,early diagnosis is difficult and depends predominantly on neonatal screening.Therefore,the aim of this study was to explore routine biomarkers for X-CGD in children and provide clues for early diagnosis.The cases of 10 children with X-CGD diagnosed at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from 2013 to 2016 and 122 Chinese children with X-CGD reported in the literature were summarized.Serum biomarkers and clinical symptoms at acute infection were organized.A total of 132 children with X-CGD were enrolled in this study.For 55.8%of the patients,the diagnosis was delayed more than one year after the onset of the first symptoms because no typical clinical symptoms manifested.Children with X-CGD at an acute infection stage showed three recurrent signs in temis of serum biomarkers:(1)the total number of white blood cells(especially N%)was in creased significantly,accompanied by anemia in some cases;(2)C-reactive protein(CRP)levels were increased significantly;and(3)most of the patients exhibited very high serum IgG levels(>12 g/L).Diagnosis of X-CGD at an early age is difficult because of its nonspecific clinical features.Our study suggested children with X-CGD suffering acute infection show increases in three typical serum biomarkers,which can provide clues for early diagnosis.

A novel deletion mutation of ATP7A gene in a Chinese family with Menkes disease

Menkes disease is a rare X-linked recessive .hereditary disorder first described by Menkes et al in 1962.1 including The gene mutation results in clinical features pili torti, unusual facies, mental/growth retardation and metabolic dysfunction. The pathogenic gene ATP7A was identified in 1993.2 It is located on chromosome X and encodes a transmembrane Cu^2＋ transporter. Here we reported the clinical manifestations and results of genetic study of a family with Menkes disease. In this family, a deletion mutation in ATP7A gene is responsible for the disease.

Identification of a new isoform of the murine Sh2d1a gene and its functional implications

Signaling lymphocytic activation molecule （SLAM）-associated protein （SAP） is a Src homology （SH） domain 2-containing in- tracellular adaptor protein that is predominantly expressed in the hematopoietic system by T lymphocytes and NK cells. SAP protein is encoded by the SH2DIA gene located on the X chromosome. Loss-of-function mutations in SAP cause the X-linked lymphoproliferative disease （XLP）, a severe immunodeficiency characterized by heightened susceptibility to Epstein-Barr vi- rus and impaired humoral immunity. Normal individuals express several functional and non-functional isoforms of SAP as a result of alternative splicing. In this study, we identify a cryptic exon in the murine Sh2dla gene. At the mRNA level, the new isoform of SAP （SAP-2） that includes this new exon is widely expressed in lymphoid tissues by C57BL/6 and 129 strains of inbred mice. SAP-2 accounts for approximately 1%-3% of total SAP transcripts, and it is dynamically regulated during lym- phocyte activation. At the protein level, the SAP-2 isoform is a 144 amino-acid protein. Compared to the dominant 126 ami- no-acid SAP-I isoform, the additional 18 amino acids are inserted into a structural region that is critical for phosphotyrosine binding. Our functional analysis in vitro indicates that SAP-2 is a non-functional isoform due to decreased protein stability. Thus, both human and mouse have multiple SAP splice isoforms that may or may not function. Modulation of relative propor- tions of these isoforms is potentially a mechanism whereby cells can regulate SAP-mediated biological activities.