High diagnostic yield and novel variants in very late-onset spasticity.
Momen AlmomenKristina MartensAsfia QuadirCarly Sabine PontifexAlexandra HansonLawrence KorngutGerald PfefferPublished in: Journal of neurogenetics (2019)
Hereditary spastic paraplegias (HSPs) are a diverse group of genetic conditions with variable severity and onset age. From a neurogenetic clinic, we identified 14 patients with very late-onset HSP, with symptoms starting after the age of 35. In this cohort, sequencing of known genetic causes was performed using clinically available HSP sequencing panels. We identified 4 patients with mutations in SPG7 and 3 patients with SPAST mutations, representing 50% of the cohort and indicating a very high diagnostic yield. In the SPG7 group, we identified novel variants in two patients. We have also identified two novel mutations in the SPAST group. We present sequencing data from cDNA and RT-qPCR to support the pathogenicity of these variants, and provide observations regarding the poor genotype-phenotype correlation in these conditions that should be the subject of future study.
Keyphrases
- late onset
- copy number
- early onset
- heat shock
- single cell
- end stage renal disease
- heat shock protein
- genome wide
- ejection fraction
- heat stress
- newly diagnosed
- chronic kidney disease
- botulinum toxin
- spinal cord injury
- cerebral palsy
- primary care
- peritoneal dialysis
- prognostic factors
- oxidative stress
- current status
- staphylococcus aureus
- physical activity
- gene expression
- pseudomonas aeruginosa