A novel nonsense variant in the ATL3 gene is associated with disturbed pain sensitivity, numbness of distal limbs and muscle weakness

Abstract

IntroductionHereditary sensory neuropathy (HSN) describes as a heterogeneous group of peripheral neuropathies. HSN type 1 (HSN1) is one subtype characterized by distal sensory impairment that occurs in the form of numbness, tingling, or pain. To date, only two variants in the atlastin GTPase 3 (ATL3) gene have been identified that result in hereditary sensory neuropathy type 1F (HSN1F) with autosomal dominantinheritance. MethodsWe sudied and examined who present with sensory disturbances and muscle weakness in their lower limb. Patients underwent Whole Exome Sequencing and Sanger sequencing was performed in families for validation of detected variant. ResultsHere, we identified two Iranian families carrying the novel heterozygous stop variant NM_015459.5: c.16C>T, p.Arg6Ter in ATL3 that led to disturbed pain and touch sensitivity. This variant in the ATL3 gene was detected in both families (NM_015459.5: c.16C>T, p.Arg6Ter) by whole‐exome sequencing and confirmed by Sanger sequencing. ConclusionIn this study, the subjects manifested weakness of distal limb muscles and numbness of the lower extremities. In addition, some unusual features, including hearing problems and inability to sit and walk presented in one of the patients. Eventually, we provide a case‐based review of the clinical features associated with HSN1F. Hitherto, only 11 patients with HSN1F have been reported. We compared our findings to previously reported cases, suggesting that the clinical features are generally variable in the HSN1F patients.

The First Large Deletion of ATL3 Identified in a Patient Presenting with a Sensory Polyneuropathy

“…NGS analysis did not reveal any other possible pathogenic variation that could explain the patient's symptoms. patient presented in this study developed typical HSN1F clinical symptoms, such as sensory troubles limited to lower limbs, paresthesia, and altered tendon reflexes, which could be compatible with a variation in ATL3, such as those described in previous studies presenting point mutations in ATL3 [5,[12][13][14][15].…”

“…Moreover, for both Bosnian and Chinese families, patients’ electrophysiologic studies showed decreased amplitude of sensory nerves and slightly reduced sensory nerve conduction velocities, suggesting an axonal degeneration of the distal sensory nerves [ 12 , 13 ]. Recently, a novel nonsense variant (c.16C > T, p.Arg6*) in ATL3 has been described in two Iranian families presented with distal impairment of sensory function disturbing superficial touch in the soles and absence of any neuropathic symptom in the upper limbs [ 15 ].…”

Reovirus infection induces transcriptome-wide unique A-to-I editing changes in the murine fibroblasts

“…We also have observed a shift in editing targets, where the same gene is being edited in control and infection, but at a different position. For instance, the Atl3 gene associated with cellular integrity and cytokinesis (Mohammadi et al, 2023) has only one edited site in 3’UTR at positions 7538115 and 7535531 in control and muReoV respectively. One explanation for that phenomenon could be that RNA editing is condition-specific (Liew et al, 2017), and/or reflect the effect of other unknown factors that regulate host-virus interactions (Piontkivska et al, 2021).…”