Neuropathy, Hereditary Motor, With Myopathic Features (VWA1)
| Dred_ID | RD00028 |
| OMIM ID | 619216 |
| Disease name | Neuropathy, Hereditary Motor, With Myopathic Features |
| Alternative names | HMNMYO |
| Category | Genetic diseases |
| Phenotype | OMIM: Hereditary motor neuropathy with myopathic features (HMNMYO) is an autosomal recessive disorder with both myopathic and neurogenic features. Affected individuals usually present in the first decade with lower leg weakness resulting in difficulty climbing stairs and problems standing on the heels. Some patients have later onset well into the adult years. Most patients have foot deformities, and some may have leg muscle atrophy. The disorder is slowly progressive and often involves the upper limbs. Muscle biopsy and electrophysiologic studies are consistent with both a myopathic process and an axonal motor neuropathy. Sensory abnormalities are not typically present, and patients remain ambulatory. The phenotype shows some phenotypic overlap with distal hereditary motor neuropathy (see, e.g., 182960), but is distinguished by the presence of myopathic features (summary by Deschauer et al., 2021 and Pagnamenta et al., 2021). (619216) (Updated 29-Dec-2021). MalaCards based summary : Neuropathy, Hereditary Motor, with Myopathic Features, is also known as hmnmyo. An important gene associated with Neuropathy, Hereditary Motor, with Myopathic Features is VWA1 (Von Willebrand Factor A Domain Containing 1). Affiliated tissues include skeletal muscle and tongue, and related phenotypes are flexion contracture and emg: myopathic abnormalities. |
| Miscellaneouse | slowly progressive variable severity variable age at onset (range first to fifth decade) |
| Prevalence | N/A [source: MalaCards] |
| Inheritance | autosomal recessive |
| Anticipation | Yes |
| Evidence | Weak |
| Gene symbol | VWA1 |
| Alias symbols | WARP; HMNMYO |
| Gene name | von Willebrand factor A domain containing 1 |
| Gene map locus | 1p36.33; chr1:1,434,861-1,442,882(+) |
| Ensembl Gene ID | ENSG00000179403 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | VWA1 belongs to the von Willebrand factor (VWF; MIM 613160) A (VWFA) domain superfamily of extracellular matrix proteins and appears to play a role in cartilage structure and function |
| Repeat unit | GGCGCGGAGC |
| Normal repeat copies | 2 |
| Pathogenic repeat copies | ≥3 |
| Gene | VWA1 |
| Repeat location | CDS |
| Chromosome locus | chr1:1435137-1435157 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | Protein |
| Possible toxicity | The major disease-associated allele in VWA1 involves an insertion of GGCGCGGAGC at the end of exon 1. According to the global allele frequency in gnomAD v3, the high frequency of this founder mutation is comparable with other well-known variants seen in related autosomal-recessive conditions |
| Pathway annotation | Reactome, KEGG |
| PMID | 33559681 |
| Authors | Alistair T Pagnamenta, Rauan Kaiyrzhanov, Yaqun Zou, et al |
| Title | An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy |
| Journal | Brain |
| Year | 2021 |