HMNR7_VWA1
- Gene
- VWA1
- Disease
- HMNR7
- Inheritance
- AR
- Classification
- Definitive
- Total Score
- 12.5
- Publications Reviewed
- 3
- Publication Span
- 3.08 years
- Last Updated
- 08/14/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt, Harriet Dashnow
Description
Biallelic VWA1 variants cause autosomal recessive hereditary motor neuropathy/neuromyopathy (HMNR7). The recurrent exon 1 10-bp repeat expansion c.62_71dup, p.(Gly25ArgfsTer74), is the predominant disease-associated allele and was reported in most families, often with loss-of-function consequences. Genetic support includes multiple unrelated affected families, trans/inheritance evidence for compound heterozygotes, and founder-haplotype/autozygosity evidence. Experimental support is mainly gene-level or patient-tissue evidence: WARP/VWA1 is an extracellular-matrix protein reported to interact with collagen VI and perlecan, and patient-derived blood or muscle tissue studies show neuromuscular biomarker/pathology changes.
Genetic evidence
Total: 12
| Singular Evidence | Probands | PMID:33559681 | 6 | 17 affected individuals from 15 unrelated families with biallelic VWA1 variants; the exon 1 10-bp repeat expansion c.62_71dup, p.(Gly25ArgfsTer74), was present in 14/15 families and homozygous in 10/15. |
| Collective Evidence | Segregation | PMID:33559681 | 1.5 | Segregation support included trans confirmation for compound-heterozygous cases by allele-specific PCR, Nanopore sequencing, or parental inheritance, plus an extended consanguineous family in which a homozygous VWA1 frameshift variant lay in a shared autozygous region spanning VWA1. No formal LOD score was reported. |
| Singular Evidence | Probands | PMID:39502942 | 6 | Cohort study identifying biallelic VWA1 variants in affected individuals with consistent neuromuscular phenotype; includes clinical, neurophysiological, and biopsy data. 12 affected individuals had the c.62_71dup, an increase from 2 to 3 GGCGCGGAGC motifs. An additional 11 novel VWA1 variants were identified in the cohort. One familiy from this study overlaps with the previous pmid:33559681 cohort. |
Experimental evidence
Total: 0.5
| Function | Protein interaction | PMID:38652110 | 0.5 | Gene-level evidence only: WARP/VWA1 is described as an extracellular-matrix protein expressed in muscle and peripheral nerve that interacts with collagen VI and perlecan; this paper did not perform a tandem-repeat/locus-specific interaction assay. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.