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.
- 2.Bassuk AG, Wallace RH, Buhr A, Buller AR, Afawi Z, Shimojo M, Miyata S, Chen S, Gonzalez-Alegre P, Griesbach HL, Wu S, Nashelsky M, Vladar EK, Antic D, Ferguson PJ, Cirak S, Voit T, Scott MP, Axelrod JD, Gurnett C, Daoud AS, Kivity S, Neufeld MY, Mazarib A, Straussberg R, Walid S, Korczyn AD, Slusarski DC, Berkovic SF, El-Shanti HI (2008) A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome. Am J Hum Genet 83(5):572–581. https://doi.org/10.1016/j.ajhg.2008.10.003 CrossRefGoogle Scholar
- 3.Baselt RC (2017) Disposition of toxic drugs and chemicals in man, 11th edn. Biomedical Publications, CaliforniaGoogle Scholar
- 5.Moretti S, Armougom F, Wallace IM, Higgins DG, Jongeneel CV, Notredame C (2007) The M-coffee web server: a meta-method for computing multiple sequence alignments by combining alternative alignment methods. Nucleic Acids Res 35(Web Server issue):W645–W648. https://doi.org/10.1093/nar/gkm333 CrossRefGoogle Scholar
- 6.Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–423. https://doi.org/10.1038/gim.2015.30 https://www.nature.com/articles/gim201530#supplementary-information CrossRefGoogle Scholar
- 8.Tao H, Manak JR, Sowers L, Mei X, Kiyonari H, Abe T, Dahdaleh NS, Yang T, Wu S, Chen S, Fox MH, Gurnett C, Montine T, Bird T, Shaffer LG, Rosenfeld JA, McConnell J, Madan-Khetarpal S, Berry-Kravis E, Griesbach H, Saneto RP, Scott MP, Antic D, Reed J, Boland R, Ehaideb SN, El-Shanti H, Mahajan VB, Ferguson PJ, Axelrod JD, Lehesjoki A-E, Fritzsch B, Slusarski DC, Wemmie J, Ueno N, Bassuk AG (2011) Mutations in prickle orthologs cause seizures in flies, mice, and humans. Am J Hum Genet 88(2):138–149. https://doi.org/10.1016/j.ajhg.2010.12.012 CrossRefGoogle Scholar
- 10.Paemka L, Mahajan VB, Ehaideb SN, Skeie JM, Tan MC, Wu S, Cox AJ, Sowers LP, Gecz J, Jolly L, Ferguson PJ, Darbro B, Schneider A, Scheffer IE, Carvill GL, Mefford HC, El-Shanti H, Wood SA, Manak JR, Bassuk AG (2015) Seizures are regulated by ubiquitin-specific peptidase 9 X-linked (USP9X), a de-ubiquitinase. PLoS Genet 11(3):e1005022. https://doi.org/10.1371/journal.pgen.1005022 CrossRefGoogle Scholar
- 11.Todd BP, Bassuk AG (2018) A de novo mutation in PRICKLE1 associated with myoclonic epilepsy and autism spectrum disorder. J Neurogenet:1–3. https://doi.org/10.1080/01677063.2018.1473862
- 13.Assenza G, Benvenga A, Gennaro E, Tombini M, Campana C, Assenza F, Di Pino G, Di Lazzaro V (2017) A novel c132-134del mutation in Unverricht-Lundborg disease and the review of literature of heterozygous compound patients. Epilepsia 58(2):e31–e35. https://doi.org/10.1111/epi.13626 CrossRefGoogle Scholar
- 15.Barsi P, Kenez J, Solymosi D, Kulin A, Halasz P, Rasonyi G, Janszky J, Kaloczkai A, Barcs G, Neuwirth M, Paraicz E, Siegler Z, Morvai M, Jerney J, Kassay M, Altmann A (2000) Hippocampal malrotation with normal corpus callosum: a new entity? Neuroradiology 42(5):339–345. https://doi.org/10.1007/s002340050895 CrossRefGoogle Scholar
- 17.Blümcke I, Thom M, Aronica E, Armstrong DD, Bartolomei F, Bernasconi A, Bernasconi N, Bien CG, Cendes F, Coras R, Cross JH, Jacques TS, Kahane P, Mathern GW, Miyata H, Moshé SL, Oz B, Özkara Ç, Perucca E, Sisodiya S, Wiebe S, Spreafico R (2013) International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a task force report from the ILAE commission on diagnostic methods. Epilepsia 54(7):1315–1329. https://doi.org/10.1111/epi.12220 CrossRefGoogle Scholar