Sudden unexpected death with rare compound heterozygous variants in PRICKLE1
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Progressive myoclonus epilepsy-ataxia syndrome (EPM5) is an autosomal recessive form of progressive myoclonus epilepsy that has been associated with a homozygous missense mutation in PRICKLE1. We report a 23-year-old male who died shortly after refractory convulsion and respiratory failure. Autopsy showed unilateral hippocampal malformation without significant neuronal loss or gliosis. Genetic analysis that targeted both epilepsy and cardiac disease using next-generation sequencing revealed two variants of PRICKLE1. Additional investigation showed that the patient’s father (p.Asp760del) and mother (p.Asp201Asn) each had a mutation in this gene. The present case shows that EPM5 can also be caused by compound heterozygous mutations.
KeywordsCompound heterozygous mutation Hippocampus Neuropathology PRICKLE1 Progressive myoclonus epilepsy Sudden death
The authors thank Ms. Tamae Sasakura, Mr. Noboru Onozuka, Ms. Syuko Matsumori and Mr. Osamu Yamamoto for their technical assistance. We thank Natasha Beeton-Kempen, PhD, and Adam Phillips, PhD from Edanz Group (www.edanzediting.com/ac) for editing a draught of this manuscript.
This report was supported in part by The Uehara Memorial Foundation to N.N., JSPS KAKENHI Grant Numbers JP18k10119 to Y.H and JP17k09263 to N.N.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Written consent was obtained from family members before the genetic study. The ethical committee of Toyama University approved this study, which was performed in accordance with the ethical standards established in the 1964 Declaration of Helsinki.
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