The First Large Deletion of <i>ATL3</i> Identified in a Patient Presenting with a Sensory Polyneuropathy
Hereditary sensory neuropathies (HSN) are a heterogenous group of sensory neuropathies. Mutations in <i>ATL3</i> have been described in patients presenting with hereditary sensory neuropathy IF (HSN1F), a subtype of HSN. Herein, by analyzing targeted-NGS data of a patient presenting with...
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MDPI AG
2023-05-01
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| author | Ioanna Pyromali Laurence Richard Paco Derouault Jean-Michel Vallat Karima Ghorab Corinne Magdelaine Franck Sturtz Frédéric Favreau Anne-Sophie Lia |
| author_facet | Ioanna Pyromali Laurence Richard Paco Derouault Jean-Michel Vallat Karima Ghorab Corinne Magdelaine Franck Sturtz Frédéric Favreau Anne-Sophie Lia |
| author_sort | Ioanna Pyromali |
| collection | DOAJ |
| description | Hereditary sensory neuropathies (HSN) are a heterogenous group of sensory neuropathies. Mutations in <i>ATL3</i> have been described in patients presenting with hereditary sensory neuropathy IF (HSN1F), a subtype of HSN. Herein, by analyzing targeted-NGS data of a patient presenting with sensory neuropathy symptoms using the CovCopCan bioinformatic tool, we discovered the presence of a deletion of around 3kb in <i>ATL3</i> from Chr11:63,401,422 to Chr11:63,398,182. This deletion affects <i>ATL3</i> exons 11 and 12 and could lead to the mutation c.(1036-861_1539+329del), p.(Ala346_Gln513del). In addition, an analysis of the breakpoints’ sequences revealed the presence of Alu transposable elements at the position of the breakpoints, which pointed to a possible erroneous recombination event following a non-allelic-homologous-recombination mechanism in this area. Moreover, electronic microscopy analysis of the patient’s nerve biopsy revealed a severe rarefaction of the myelinated fibers, a demyelinating–remyelinating process, and an abnormal aspect of the endoplasmic reticulum. These findings suggest that this structural variation could potentially be responsible for the HSN symptoms of the patient. Research of structural variations in <i>ATL3</i> in numerous other patients presenting similar symptoms should be broadly investigated in order to improve patients’ diagnoses. |
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| publishDate | 2023-05-01 |
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| series | Biomedicines |
| spelling | doaj.art-38396eaa0d3e49e9a51bb45d20ac9caa2023-11-18T09:25:07ZengMDPI AGBiomedicines2227-90592023-05-01116156510.3390/biomedicines11061565The First Large Deletion of <i>ATL3</i> Identified in a Patient Presenting with a Sensory PolyneuropathyIoanna Pyromali0Laurence Richard1Paco Derouault2Jean-Michel Vallat3Karima Ghorab4Corinne Magdelaine5Franck Sturtz6Frédéric Favreau7Anne-Sophie Lia8UR 20218, NeurIT, Faculty of Medicine and Pharmacy, University of Limoges, F-87000 Limoges, FranceService de Neurologie, Centre Hospitalier Universitaire (CHU) Limoges, F-87000 Limoges, FranceService de Bioinformatique, Centre Hospitalier Universitaire (CHU) Limoges, F-87000 Limoges, FranceService de Neurologie, Centre Hospitalier Universitaire (CHU) Limoges, F-87000 Limoges, FranceService de Neurologie, Centre Hospitalier Universitaire (CHU) Limoges, F-87000 Limoges, FranceUR 20218, NeurIT, Faculty of Medicine and Pharmacy, University of Limoges, F-87000 Limoges, FranceUR 20218, NeurIT, Faculty of Medicine and Pharmacy, University of Limoges, F-87000 Limoges, FranceUR 20218, NeurIT, Faculty of Medicine and Pharmacy, University of Limoges, F-87000 Limoges, FranceUR 20218, NeurIT, Faculty of Medicine and Pharmacy, University of Limoges, F-87000 Limoges, FranceHereditary sensory neuropathies (HSN) are a heterogenous group of sensory neuropathies. Mutations in <i>ATL3</i> have been described in patients presenting with hereditary sensory neuropathy IF (HSN1F), a subtype of HSN. Herein, by analyzing targeted-NGS data of a patient presenting with sensory neuropathy symptoms using the CovCopCan bioinformatic tool, we discovered the presence of a deletion of around 3kb in <i>ATL3</i> from Chr11:63,401,422 to Chr11:63,398,182. This deletion affects <i>ATL3</i> exons 11 and 12 and could lead to the mutation c.(1036-861_1539+329del), p.(Ala346_Gln513del). In addition, an analysis of the breakpoints’ sequences revealed the presence of Alu transposable elements at the position of the breakpoints, which pointed to a possible erroneous recombination event following a non-allelic-homologous-recombination mechanism in this area. Moreover, electronic microscopy analysis of the patient’s nerve biopsy revealed a severe rarefaction of the myelinated fibers, a demyelinating–remyelinating process, and an abnormal aspect of the endoplasmic reticulum. These findings suggest that this structural variation could potentially be responsible for the HSN symptoms of the patient. Research of structural variations in <i>ATL3</i> in numerous other patients presenting similar symptoms should be broadly investigated in order to improve patients’ diagnoses.https://www.mdpi.com/2227-9059/11/6/1565hereditary sensory neuropathystructural variation<i>ATL3</i>NGSCovCopCan |
| spellingShingle | Ioanna Pyromali Laurence Richard Paco Derouault Jean-Michel Vallat Karima Ghorab Corinne Magdelaine Franck Sturtz Frédéric Favreau Anne-Sophie Lia The First Large Deletion of <i>ATL3</i> Identified in a Patient Presenting with a Sensory Polyneuropathy Biomedicines hereditary sensory neuropathy structural variation <i>ATL3</i> NGS CovCopCan |
| title | The First Large Deletion of <i>ATL3</i> Identified in a Patient Presenting with a Sensory Polyneuropathy |
| title_full | The First Large Deletion of <i>ATL3</i> Identified in a Patient Presenting with a Sensory Polyneuropathy |
| title_fullStr | The First Large Deletion of <i>ATL3</i> Identified in a Patient Presenting with a Sensory Polyneuropathy |
| title_full_unstemmed | The First Large Deletion of <i>ATL3</i> Identified in a Patient Presenting with a Sensory Polyneuropathy |
| title_short | The First Large Deletion of <i>ATL3</i> Identified in a Patient Presenting with a Sensory Polyneuropathy |
| title_sort | first large deletion of i atl3 i identified in a patient presenting with a sensory polyneuropathy |
| topic | hereditary sensory neuropathy structural variation <i>ATL3</i> NGS CovCopCan |
| url | https://www.mdpi.com/2227-9059/11/6/1565 |
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