Dataset Information

A novel TFG variant of uncertain significance in amyotrophic lateral sclerosis: A case report and review of literature.

ABSTRACT:

Introduction

Amyotrophic lateral sclerosis is a neurodegenerative disease with wide variation of genetics associated with it. Among the different genes described, mutation in TFG is a rare finding in amyotrophic lateral sclerosis.

Case presentation

A 35 years old right-handed male presenting with ipsilateral weakness was diagnosed with amyotrophic lateral sclerosis. He was found to have missense variant of TFG with uncertain significance on exome sequencing.

Clinical discussion

The genetics involved in amyotrophic lateral sclerosis is ever-evolving. The identification of new TFG variant in this disease adds another evidence to the role of TFG in neurodegenerative disease.

Conclusions

The finding of TFG variant of uncertain significance is a rare finding in amyotrophic lateral sclerosis. And with the identification of new TFG variant, it leads to further understanding of spectrum of TFG and its pathophysiology in amyotrophic lateral sclerosis.

SUBMITTER: Dhakal B

PROVIDER: S-EPMC9793128 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

A novel TFG variant of uncertain significance in amyotrophic lateral sclerosis: A case report and review of literature.

Dhakal Bishal B Sapkota Sachin S Parajuli Aakriti A Khadka Bibek B Subedi Binaya B Paudel Raju R Thapa Rohit R Rimal Sabin S

Annals of medicine and surgery (2012) 20221107

<h4>Introduction</h4>Amyotrophic lateral sclerosis is a neurodegenerative disease with wide variation of genetics associated with it. Among the different genes described, mutation in TFG is a rare finding in amyotrophic lateral sclerosis.<h4>Case presentation</h4>A 35 years old right-handed male presenting with ipsilateral weakness was diagnosed with amyotrophic lateral sclerosis. He was found to have missense variant of TFG with uncertain significance on exome sequencing.<h4>Clinical discussion ...[more]

PMID: 36582889

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Project description:Schwann cells are essential for the maintenance and function of motor neurons, axonal networks, and the neuromuscular junction. In amyotrophic lateral sclerosis, where motor neuron function is progressively lost, Schwann cell function may also be impaired. Recently, important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported. This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles, marking, to our knowledge, the first instance of such treatment. An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis. After initial diagnosis, the patient underwent a combination of generic riluzole, sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis, and taurursodiol. The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function. We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired (senescent) and that exposure of the patient's Schwann cells to allogeneic Schwann cell-derived exosomal vesicles, cultured expanded from a cadaver donor improved their growth capacity in vitro. After a period of observation lasting 10 weeks, during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored, the patient received weekly consecutive infusions of 1.54 × 10 12 (×2), and then consecutive infusions of 7.5 × 10 12 (×6) allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco's phosphate-buffered saline. None of the infusions were associated with adverse events such as infusion reactions (allergic or otherwise) or changes in vital signs. Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend. A more sensitive in-house assay suggested possible inflammasome activation during the disease course. A trend for clinical stabilization was observed during the infusion period. Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles. Initial findings suggest that this approach is safe.

Dataset Information

A novel TFG variant of uncertain significance in amyotrophic lateral sclerosis: A case report and review of literature.

Introduction

Case presentation

Clinical discussion

Conclusions

Publications

A novel TFG variant of uncertain significance in amyotrophic lateral sclerosis: A case report and review of literature.

Similar Datasets

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