Abstract
Purpose: Progressive myoclonus epilepsy (PME) comprises a group of heterogeneous disorders defined by the combination of action myoclonus, epileptic seizures, and progressive neurologic deterioration. Neurologic deterioration may include progressive cognitive decline, ataxia, neuropathy, and myopathy. A number of genes have been identified to cause either isolated PME or diseases that manifest PME. We report a Saudi family with a very rare form of autosomal dominant PME.
Methods: We included two patients from Saudi Arabia with a presumptive clinical diagnosis of PME. The patients were from a family with an affected mother 1-2 and two affected siblings proband II-3 and II-4 (a girl and a boy).
Results: Genetic analysis revealed a single variant in the PRICKLE1 gene NM_153026.2: c.251 G > A (p.Arg84Gln). Segregation study was performed using DNA from the parents and two sisters. The same variant was identified in one affected parent (the mother 1-2) and the two unaffected sisters II-1 and II-2 while it was absent from the unaffected father I-1.
Conclusion: This gene was linked to both autosomal dominant and autosomal recessive PME. To our best knowledge, this is the first report that demonstrates a single PRICKLE1 pathogenic variant segregating with PME in one family. The novel variant identified in this family has never been previously reported as a disease-causing variant. The presence of the same variant in the unaffected individuals may suggest that heterozygous mutations in the PRICKLE1 gene have incomplete penetrance. Further research is needed to elucidate the penetrance of heterozygous mutations in the PRICKLE1 gene.