Clinical and Genetic Study on a Chinese Patient with Infantile Onset Epileptic Encephalopathy carrying a PPP3CA Null Variant: a case report

Sai Yang,Liming Yang,Shulei Liu,Qingyun Kang,Zeshu Ning,Zhenhua Cao,Xiang Shen,Hongmei Liao,Xiaojun Kuang

doi:10.1186/s12887-020-02213-7

Abstract

BackgroundPPP3CA gene encodes the catalytic subunit A of a calcium-dependent protein phosphatase called calcineurin. However, two distinct mechanisms in PPP3CA deficiency would cause two clinically different diseases. Gain-of-function mutations in the autoinhibitory domain at the C-terminus would cause ACCIID that stands for arthrogryposis, cleft palate, craniosynostosis and impaired intellectual development. While loss-of-function mutations in PPP3CA would cause infantile or early childhood onset epileptic encephalopathy1, named as IECEE1. IECEE1 is a severe epileptic neurodevelopmental disorder and mainly characterized by psychomotor delay. Here, we report a Chinese patient who was clinically and genetically diagnosed as IECEE1. We also extensively analyzed electroencephalogram (EEG) features of the patient in this study.Case presentationA 2-year-old Chinese patient who had recurrent polymorphic seizures was clinically and genetically diagnosed as IECEE1. A frameshift variant c.1283insC (p.T429NfsX22) was identified in this case. Multiple types of abnormal features were observed in the EEG, comparing with the previous reports.ConclusionsThese findings could expand the spectrum of PPP3CA mutations and might also support the diagnosis and further study of IECEE1.

Highlights

PPP3CA gene encodes the catalytic subunit A of a calcium-dependent protein phosphatase called calcineurin
These findings could expand the spectrum of PPP3CA mutations and might support the diagnosis and further study of Infantile or early childhood onset epileptic encephalopathy1 (IECEE1)
Infantile or early childhood onset epileptic encephalopathy1 (IECEE1, OMIM#617711) and arthrogryposis, cleft palate, craniosynostosis, impaired intellectual development (ACCIID, OMIM#618265) are two autosomal dominant diseases caused by mutations in PPP3CA gene

Summary

Introduction

PPP3CA gene encodes the catalytic subunit A of a calcium-dependent protein phosphatase called calcineurin. Background Infantile or early childhood onset epileptic encephalopathy1 (IECEE1, OMIM#617711) and arthrogryposis, cleft palate, craniosynostosis, impaired intellectual development (ACCIID, OMIM#618265) are two autosomal dominant diseases caused by mutations in PPP3CA gene. Patients with IECEE1 present refractory seizures with varying onset age, and some of them have hypotonia or visual disorders [1]. While other missense mutations or null variants (including nonsense and frameshift mutations) might damage the function of PPP3CA, resulting in IECEE1 [2].

Results

Conclusion