A Case of Distal Hereditary Motor Neuronopathy‐7 With Two Novel <scp> <i>VWA1</i> </scp> Variants in Compound Heterozygosity
ABSTRACT Distal hereditary motor neuronopathy‐7 (HMNR7) is an autosomal recessive VWA1‐related disorder characterized predominantly by distal motor involvement. A 41‐year‐old man with a history of childhood orthopedic surgery for foot deformities exhibited progressive distal weakness and muscle atrophy with lower limb predominance. Electrophysiological studies showed axonal sensorimotor involvement. Whole‐genome sequencing identified two novel VWA1 variants in compound heterozygosity: c.1244 T>C [p.(L415P)], located in the fibronectin type III (FN3) domain, and c.455delG [p.(G152Afs*54)]. This report underscores the importance of comprehensive genome analysis including VWA1 in patients with distal neuropathies, particularly when early‐onset foot deformities are present, and highlights the potential pathogenic relevance of missense variants within the second FN3 domain.
Authors
- Kenta Orimo (ORCID: https://orcid.org/0000-0003-3649-5570)
- J Mitsui
- Toshiyuki Kakumoto (ORCID: https://orcid.org/0000-0002-1147-9454)
- Takashi Matsukawa (ORCID: https://orcid.org/0000-0002-5925-9450)
- Shoji Tsuji
Institutions
- University of Tokyo Hospital (JP)
- The University of Tokyo (JP)
- International University of Health and Welfare (JP)
Publication Details
- Journal
- Neurology and Clinical Neuroscience
- Published
- 2026-07-17
- DOI
- https://doi.org/10.1002/ncn3.70142
- Primary Topic
- Hereditary Neurological Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Japan Agency for Medical Research and Development
- Japan Society for the Promotion of Science