Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy

We discuss a case of a 58 year old male who presented for left upper extremity steal syndrome including ischemic monomelic neuropathy (IMN) 1.5 months after arteriovenous fistula creation. He presented after three surgical attempts to salvage his fistula with rest pain, complete loss of function with contracture of the 4th and 5th digits, and loss of sensation in the ulnar distribution for more than three weeks. At our institution, he underwent surgical ligation of the distal fistula and creation of a new fistula proximally, resulting in complete resolution of his vascular steal symptoms almost immediately despite the chronicity prior to surgical presentation. Our patient provides a unique perspective regarding dialysis access salvage versus patient quality of life. The patients’ functional status and pain levels should take precedence over salvage of an arteriovenous access site, and early ligation of the access should be completed prior to chronic IMN development. However, if a patient presents late along the IMN course, we recommend strong consideration of access ligation in order to attempt to regain the full neurovascular function of the extremity as we experienced in our patient.

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Celecoxib Inhibits Helicobacter pylori-induced Invasion of Gastric Cancer Cells Through an Adenine Nucleotide Translocator-Dependent Mechanism

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/18715206113139990324 ◽

2013 ◽

Vol 13 (8) ◽

pp. 1267-1272 ◽

Cited By ~ 3

Author(s):

Chunhui Lan ◽

Liuqin Yang ◽

Lilin Fan ◽

Yafei Zhang ◽

Jun Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Cells ◽

Adenine Nucleotide ◽

Adenine Nucleotide Translocator ◽

Gastric Cancer Cells ◽

Dependent Mechanism

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Differential expression of adenine nucleotide translocator isoforms in mammalian tissues and during muscle cell differentiation.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)42082-0 ◽

1992 ◽

Vol 267 (21) ◽

pp. 14592-14597 ◽

Cited By ~ 2

Author(s):

G Stepien ◽

A Torroni ◽

A.B. Chung ◽

J.A. Hodge ◽

D.C. Wallace

Keyword(s):

Cell Differentiation ◽

Differential Expression ◽

Muscle Cell ◽

Adenine Nucleotide ◽

Adenine Nucleotide Translocator ◽

Muscle Cell Differentiation ◽

Mammalian Tissues

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Molecular characterisation of rare loss-of-function NPAS3 and NPAS4 variants identified in individuals with neurodevelopmental disorders

Scientific Reports ◽

10.1038/s41598-021-86041-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Joseph J. Rossi ◽

Jill A. Rosenfeld ◽

Katie M. Chan ◽

Haley Streff ◽

Victoria Nankivell ◽

...

Keyword(s):

Neurodevelopmental Disorders ◽

Protein Function ◽

Transcriptional Activity ◽

Neurodevelopmental Disorder ◽

Complete Loss ◽

Loss Of Function ◽

Targeted Disruption ◽

Clinical Exome Sequencing ◽

Partner Protein ◽

The Brain

AbstractAberrations in the excitatory/inhibitory balance within the brain have been associated with both intellectual disability (ID) and schizophrenia (SZ). The bHLH-PAS transcription factors NPAS3 and NPAS4 have been implicated in controlling the excitatory/inhibitory balance, and targeted disruption of either gene in mice results in a phenotype resembling ID and SZ. However, there are few human variants in NPAS3 and none in NPAS4 that have been associated with schizophrenia or neurodevelopmental disorders. From a clinical exome sequencing database we identified three NPAS3 variants and four NPAS4 variants that could potentially disrupt protein function in individuals with either developmental delay or ID. The transcriptional activity of the variants when partnered with either ARNT or ARNT2 was assessed by reporter gene activity and it was found that variants which truncated the NPAS3/4 protein resulted in a complete loss of transcriptional activity. The ability of loss-of-function variants to heterodimerise with neuronally enriched partner protein ARNT2 was then determined by co-immunoprecipitation experiments. It was determined that the mechanism for the observed loss of function was the inability of the truncated NPAS3/4 protein to heterodimerise with ARNT2. This further establishes NPAS3 and NPAS4 as candidate neurodevelopmental disorder genes.

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