# Genomic Analysis in Hereditary Neuropathy: Insights from a Nationwide French Cohort

Marina Konyukh, Vianney Ponsignon, Marine Guillaud-Bataille, Jean-Madeleine de Sainteagathe, Jerome Bouligand, Ariane Lunati-Rozie, Anne Sophie Lia, Emmanuelle Campana-Salort, Emilien Delmont, Ludivine Kouton, et al.

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Marina Konyukh, Vianney Ponsignon, Marine Guillaud-Bataille, Jean-Madeleine de Sainteagathe, Jerome Bouligand, et al. Genomic Analysis in Hereditary Neuropathy: Insights from a Nationwide French Cohort. Journal of the Peripheral Nervous System, 2025, 30 (3, S, SI), pp.11. hal-05467123

HAL Id: hal-05467123

https://amu.hal.science/hal-05467123v1

Submitted on 5 Feb 2026

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# Genomic Analysis in Hereditary Neuropathy: Insights from a Nationwide French Cohort

**Marina Konyukh**¹, **Vianney Ponsignon**², **Marine Guillaud-Bataille**³, **Jean-Madeleine De SainteAgathe**⁴, **Jérôme Bouligand**⁵, **Ariane Lunati-Rozie**⁶, **Anne Sophie Lia**⁷, **Emmanuelle Campana-Salort**⁸, **Emilien Delmont**⁹, **Ludivine Kouton**¹⁰, **Aude-Marie Grapperon**¹¹, **Annie Verschueren**¹², **Ariane Choumert**¹³, **Virginie Guillet-Pichon**¹⁴, **Sarah Leonard-Louis**¹⁵, **Gorka Fernandez-Eulate**¹⁶, **Edoardo Malfatti**¹⁷, **Marion Masingue**¹⁸, **Christine Vinciguerra**¹⁹, **Tanya Stojkovic**²⁰, **Shahram Attarian**²¹, **Alix De Becdelièvre**¹, **Nathalie Bonello-Palot**²²

¹Department of Genetics, Henri Mondor Hospital, Créteil, France, ²Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie, APHP. Université Paris Saclay, Paris, France, ³Hôpital Pitié-Salpétrière, Paris, France, ⁴APHP Sorbonne Université, Département de Génétique, Groupe Hospitalier Pitié-Salpétrière-Hôpital Tro, Paris, France, ⁵Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie, APHP. Université Paris Saclay, Paris, France, ⁶Department of Genetics, Henri Mondor University Hospital, APHP, Paris, France, ⁷Limoges University Hospital—University Limoges—UR 20218 NeurIT, Limoges, France, ⁸APHM, Neuromuscular Diseases Reference Center, Timone Hospital, Marseille, France, ⁹Referral centre for neuromuscular diseases and ALS, Marseille, France, ¹⁰Referral Center for ALS and Neuromuscular Diseases, Timone University Hospital, Marseille, France, ¹¹La Timone, AP-HM, Marseille, France, ¹²Refferal centre for neuromuscular diseases and ALS, Marseille, France, ¹³Neuromuscular Disease Reference Center, La Réunion, Saint-pierre, France, ¹⁴CRMR Neurogénétique, Service de Neurologie, Angers, France, ¹⁵Institut de Myologie, Paris, France, ¹⁶Pitié-Salpêtrière Hospital, Paris, France, ¹⁷Reference Center for Neuromuscular Disorders, AP-HP Henri Mondor University Hospital, University, Créteil, France, ¹⁸Neuromyologie, Paris, France, ¹⁹LBMMS GCS AURAGEN, Lyon, France, ²⁰Sorbonne University, Pitié-Salpêtrière Hospital, Institute of Myology, Paris, France, ²¹AP-HM, Marseille, France, ²²Marseille Medical Genetics, Aix-Marseille University–Inserm UMR 1251, Marseille, France

**Introduction:** Hereditary neuropathies present significant diagnostic challenges due to their clinical and genetic heterogeneity. Thanks to the national program Plan France Médecine Génomique 2025 whole-genome sequencing is now available as part of clinical care in France. The aim of this study was to assess the impact of genome sequencing on the diagnosis of hereditary neuropathies presenting before the age of 50, and to highlight the role of collaborative tools in advancing the discovery of new genes.

**Methods:** From February 2023 to December 2025, 186 genome sequencing requests were received for patients with suspected hereditary neuropathy. All patients must have undergone at least a neuropathy gene panel. 97 cases underwent the Auragen genome sequencing pipeline and 89 SeqOIA. Of these, 109 analyses were completed, 26 are ongoing, and 51 are pending initiation. GeneMatcher was used to facilitate collaborative searches for new gene-disease associations. Variant classification followed the established ACMG
guidelines.

**Results:** Of the 109 requests processed, 35 (32%) yielded a conclusive genetic diagnosis, identifying pathogenic variants in known neuromuscular-associated genes. Six cases (6%) revealed variants of uncertain significance requiring further validation. Sixty-eight cases (62%) were inconclusive, underlining the complexity of the genetic architecture of inherited neuropathies. Notably, genome sequencing has identified several new candidate genes and, in some cases, this analysis led us to revise the initial diagnosis and propose appropriate management.

**Conclusions:** This study highlights the raie of genome sequencing in reducing the number of undiagnosed patients with hereditary neuropathy. In 32% of cases, a molecular diagnosis was established through genome sequencing, a high proportion considering ail had undergone previous gene panels, thus reducing the number of patients in diagnostic odyssey. Additionally, genome sequencing has proved invaluable in identifying novel disease-associated genes. In conclusion, our nationwide French experience strongly supports the integration of genome sequencing as a diagnostic tool for hereditary neuropathies, particularly for young patients.

**References:**

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**Keywords:** Hereditary neuropathies, whole genome sequencing, diagnostic odyssey, novel genes, plan france médecine génomique 2025