STRs database » VWA1 locus
Overview of repeats
In a study by Pagnamenta and colleagues (Pagnamenta et al. (2021)), it was reported that a bi-allelic 10-bp repeat expansion (GGCGCGGAGC) in the VWA1 gene exon 1 was present in 14 out of 15 families with hereditary motor neuropathy. The mean age of onset was 2.0 ± 1.4 years. In the reference-population analysis reported by Pagnamenta and colleagues, all 89 individuals identified with the three-copy allele among 140632 individuals were heterozygous. Authors suggested that shorter allele (1 repeat) also leads to a premature stop codon and may represent a second disease-causing founder mutation at the same locus (71/136,000 heterozygous alleles were present in the reference-population data reported by the authors, but no homozygous were found).
In a further cohort of 20 individuals, Nagy et al. (2024) expanded the reported phenotype to include hypermobility, axial weakness, asymmetric involvement and, in some cases, upper motor-neuron signs. They identified additional VWA1 variants and reaffirmed the recurrent 10-bp frameshifting insertion as the most common disease-causing allele in the combined series.