AUTHOR=Li Jieling , Cao Jie 

TITLE=Case report: A novel PPP3CA truncating mutation within the regulatory domain causes severe developmental and epileptic encephalopathy in a Chinese patient

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.889167

DOI=10.3389/fneur.2022.889167

ISSN=1664-2295

ABSTRACT=<sec><title>Introduction</title><p>Developmental and epileptic encephalopathy 91 (DEE91; OMIM#<ext-link ext-link-type="DDBJ/EMBL/GenBank" xlink:href="617711" xmlns:xlink="http://www.w3.org/1999/xlink">617711</ext-link>) is a severe neurodevelopmental disorder caused by heterozygous <italic>PPP3CA</italic> variants. To the best of our knowledge, only a few DEE91 cases have been reported.</p></sec><sec><title>Results</title><p>This study reports a boy who experienced recurrent afebrile convulsions and spasms at the age of 2 months. After being given multiple antiepileptic treatments with levetiracetam, adrenocorticotropic hormone (ACTH), prednisone, topiramate, and clonazepam, his seizures were not completely relieved. At the age of 4 months, the patient exhibited delayed neuromotor development and difficulty in feeding; at the age of 6 months, he was diagnosed with developmental regression with recurrent spasms and myoclonic seizures that could respond to vigabatrin. At the age of 1 year and 4 months, the patient showed profound global developmental delay (GDD) with intermittent absence seizures. Whole-exome sequencing (WES) identified a novel loss-of-function variant c.1258_1259insAGTG (p. Val420Glufs<sup>*</sup>32) in <italic>PPP3CA</italic>.</p></sec><sec><title>Conclusion</title><p>This finding expands the genetic spectrum of the <italic>PPP3CA</italic> gene and reinforces the theory that DEE91-associated truncating variants cluster within a 26-amino acid region in the regulatory domain (RD) of <italic>PPP3CA</italic>.</p></sec>