scholarly journals T118M Variant of PMP22 Gene Presents with Painful Peripheral Neuropathy and Varying Charcot-Marie-Tooth Features: A Case Series and Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Kwo Wei David Ho ◽  
Nivedita U. Jerath
Keyword(s):  
Peripheral Neuropathy ◽  
Autosomal Recessive ◽  
Clinical Effect ◽  
Case Series ◽  
Pmp22 Gene ◽  
Loss Of Function ◽  
Review Of The Literature ◽  
Partial Loss ◽  
Charcot Marie Tooth ◽  
Electrophysiological Studies

The clinical effect of T118M variant of the PMP22 gene has been controversial. Several studies have suggested that it may be autosomal recessive, partial loss of function, or a benign variant. Here we report three cases in further support that the T118M variant of the PMP22 gene is a partial loss of function variant. These three unrelated cases were heterozygotes with the T118M variant of the PMP22 gene. All three cases presented with painful peripheral neuropathy and varying degrees of Charcot-Marie-Tooth exam features. Electrophysiological studies revealed polyneuropathy with axonal and demyelinating features in one case, but there were minimal electrophysiological changes in the other two cases. We propose that the T118M variant can cause painful peripheral neuropathy, which may be an underrecognized feature of this variant.

scholarly journals Congenital Insensitivity to Pain: A Case Report and Review of the Literature

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Leema Reddy Peddareddygari ◽  
Kinsi Oberoi ◽  
Raji P. Grewal
Keyword(s):  
Genetic Disease ◽  
Autosomal Recessive ◽  
Lumbosacral Spine ◽  
Review Of The Literature ◽  
Secondary Complications ◽  
Congenital Insensitivity ◽  
Electrophysiological Studies ◽  
Congenital Insensitivity To Pain ◽  
Insensitivity To Pain ◽  
Spine Disease

Congenital insensitivity to pain (CIP) is a rare autosomal recessive genetic disease caused by mutations in theSCN9Agene. We report a patient with the clinical features consistent with CIP in whom we detected a novel homozygous G2755T mutation in exon 15 of this gene. Routine electrophysiological studies are typically normal in patients with CIP. In our patient, these studies were abnormal and could represent the consequences of secondary complications of cervical and lumbosacral spine disease and associated severe Charcot’s joints.

scholarly journals Author response: Charcot-Marie-Tooth 2B mutations in rab7 cause dosage-dependent neurodegeneration due to partial loss of function

2013 ◽  
Author(s):  
Smita Cherry ◽  
Eugene Jennifer Jin ◽  
Mehmet Neset Özel ◽  
Zhiyuan Lu ◽  
Egemen Agi ◽  
...  
Keyword(s):  
Author Response ◽  
Loss Of Function ◽  
Partial Loss ◽  
Charcot Marie Tooth

scholarly journals SIRT2-knockdown Rescues GARS-induced Charcot-Marie-Tooth Neuropathy

2019 ◽  
Author(s):  
Chao Shen ◽  
Qian Qi ◽  
Yicai Qin ◽  
Dejian Zhou ◽  
Xinyuan Chen ◽  
...  
Keyword(s):  
Trna Synthetase ◽  
Nerve Degeneration ◽  
Loss Of Function ◽  
Wild Type ◽  
Partial Loss ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Underlying Mechanisms ◽  
Tooth Disease

AbstractCharcot-Marie-Tooth disease is the most common inherited peripheral neuropathy. Dominant mutations in glycyl-tRNA synthetase (GARS) gene cause peripheral nerve degeneration and lead to CMT disease type 2D. Mutations in GARS (GARSCMT2D) show partial loss-of-function features, suggesting that tRNA-charging deficits play a role in disease pathogenesis, but the underlying mechanisms are not fully understood. In this study we report that wild-type GARS tightly binds the NAD+-dependent deacetylase SIRT2 and inhibits its deacetylation activity, resulting in the hyperacetylated α-tubulin, the major substrate of SIRT2. Previous studies showed that acetylation of α-tubulin protects microtubules from mechanical breakage and keep axonal transportation. However, CMT2D mutations in GARS can not inhibit SIRT2 deacetylation, which leads to decrease acetylated α-tubulin and severe axonal transport deficits. Genetic reduction of SIRT2 in the Drosophila model rescues the GARS–induced axonal CMT neuropathy and extends the life span. Our findings demonstrate the pathogenic role of SIRT2-dependent α-tubulin deacetylation in mutant GARS-induced neuropathies and provide new perspectives for targeting SIRT2 as a potential therapy against hereditary axonopathies.

scholarly journals Fly model causes neurological rethink

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Madhumala K Sadanandappa ◽  
Mani Ramaswami
Keyword(s):  
Neurological Disorder ◽  
Therapeutic Approach ◽  
Loss Of Function ◽  
Partial Loss ◽  
Gain Of Function ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Drosophila Model ◽  
Tooth Disease

A Drosophila model for a neurological disorder called type 2B Charcot-Marie-Tooth disease reveals that it has its origins in a partial loss of function, rather than a gain of function, which points to the need for a new therapeutic approach.

scholarly journals Ichthyosis Follicularis with Alopecia and Photophobia Syndrome (IFAP): A Case Report and Review of the Literature

2020 ◽  
pp. 1-2
Author(s):  
Elharrouni Alaoui Aicha ◽  
◽  
Baybay Hanane ◽  
Douhi Zakia ◽  
Elloudi Sara ◽  
...  
Keyword(s):  
Case Report ◽  
Clinical Features ◽  
Autosomal Recessive ◽  
Loss Of Function ◽  
Review Of The Literature ◽  
Alopecia Universalis

IFAP syndromeis a rare autosomal recessive X-linked disease characterized by the triad of alopecia universalis, severe photophobia, and follicular ichthyosis. It is caused by loss of function of the gene MBTPS2. Its severity varies and there are only a few reports in the literature. We present a patient with characteristic clinical features

scholarly journals Novel EGR2 variant that associates with Charcot-Marie-Tooth disease when combined with lipopolysaccharide-induced TNF-α factor T49M polymorphism

2020 ◽  
Vol 6 (2) ◽  
pp. e407
Author(s):  
Maria Empar Blanco-Cantó ◽  
Nikiben Patel ◽  
Sergio Velasco-Aviles ◽  
Angeles Casillas-Bajo ◽  
Juan Salas-Felipe ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Schwann Cells ◽  
Loss Of Function ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tnf Α ◽  
Erbb Signaling ◽  
Steady State Levels ◽  
Schwann Cell Differentiation

ObjectiveTo identify novel genetic mechanisms causing Charcot-Marie-Tooth (CMT) disease.MethodsWe performed a next-generation sequencing study of 34 genes associated with CMT in a patient with peripheral neuropathy.ResultsWe found a non–previously described mutation in EGR2 (p.P397H). P397H mutation is located within the loop that connects zinc fingers 2 and 3, a pivotal domain for the activity of this transcription factor. Using promoter activity luciferase assays, we found that this mutation promotes decreased transcriptional activity of EGR2. In this patient, we also found a previously described nonpathogenic polymorphism in lipopolysaccharide-induced TNF-α factor (LITAF) (p.T49M). We show that the p.T49M mutation decreases the steady-state levels of the LITAF protein in Schwann cells. Loss of function of LITAF has been shown to produce deregulation in the NRG1-erbB signaling, a pivotal pathway for EGR2 expression by Schwann cells. Surprisingly, our segregation study demonstrates that p.P397H mutation in EGR2 is not sufficient to produce CMT disease. Most notably, only those patients expressing simultaneously the LITAF T49M polymorphism develop peripheral neuropathy.ConclusionsOur data support that the LITAF loss-of-function interferes with the expression of the transcriptional-deficient EGR2 P397H mutant hampering Schwann cell differentiation and suggest that in vivo both genes act in tandem to allow the proper development of myelin.

Immunosuppression as efficient therapy for Eosinophilic cholangitis: A case series and review of the literature

2018 ◽  
Vol 56 (01) ◽  
pp. E2-E89
Author(s):  
D Reher ◽  
C Schramm ◽  
F Brinkert ◽  
A Lohse ◽  
C Weiler-Normann
Keyword(s):  
Case Series ◽  
Review Of The Literature ◽  
Eosinophilic Cholangitis

Kindler's Syndrome with Recurrent Neutropenia: Report of Two Cases from Saudi Arabia

2020 ◽  
Author(s):  
Yousef Binamer ◽  
Muzamil A. Chisti
Keyword(s):  
Autosomal Recessive ◽  
Common Mechanism ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Skin Atrophy ◽  
Whole Exome ◽  
Infancy And Childhood ◽  
Genetics And Genomics ◽  
New Feature ◽  
Generation Sequencing

AbstractKindler syndrome (KS) is a rare photosensitivity disorder with autosomal recessive mode of inheritance. It is characterized by acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, abnormal photosensitivity, and gingival fragility. Besides these major features, many minor presentations have also been reported in the literature. We are reporting two cases with atypical features of the syndrome and a new feature of recurrent neutropenia. Whole exome sequencing analysis was done using next-generation sequencing which detected a homozygous loss-of-function (LOF) variant of FERMT1 in both patients. The variant is classified as a pathogenic variant as per the American College of Medical Genetics and Genomics guidelines. Homozygous LOF variants of FERMT1 are a common mechanism of KS and as such confirm the diagnosis of KS in our patients even though the presentation was atypical.

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