Dataset Information

Early infantile epileptic-dyskinetic encephalopathy due to biallelic PIGP mutations.

ABSTRACT: Objective:To describe clinical, biochemical, and molecular genetic findings in a large inbred family in which 4 children with a severe early-onset epileptic-dyskinetic encephalopathy, with suppression burst EEG, harbored homozygous mutations of phosphatidylinositol glycan anchor biosynthesis, class P (PIGP), a member of the large glycosylphosphatidylinositol (GPI) anchor biosynthesis gene family. Methods:We studied clinical features, EEG, brain MRI scans, whole-exome sequencing (WES), and measured the expression of a subset of GPI-anchored proteins (GPI-APs) in circulating granulocytes using flow cytometry. Results:The 4 affected children exhibited a severe neurodevelopmental disorder featuring severe hypotonia with early dyskinesia progressing to quadriplegia, associated with infantile spasms, focal, tonic, and tonic-clonic seizures and a burst suppression EEG pattern. Two of the children died prematurely between age 2 and 12 years; the remaining 2 children are aged 2 years 7 months and 7 years 4 months. The homozygous c.384del variant of PIGP, present in the 4 patients, introduces a frame shift 6 codons before the expected stop signal and is predicted to result in the synthesis of a protein longer than the wild type, with impaired functionality. We demonstrated a reduced expression of the GPI-AP CD16 in the granulocytic membrane in affected individuals. Conclusions:PIGP mutations are consistently associated with an epileptic-dyskinetic encephalopathy with the features of early infantile epileptic encephalopathy with profound disability and premature death. CD16 is a valuable marker to support a genetic diagnosis of inherited GPI deficiencies.

SUBMITTER: Vetro A

PROVIDER: S-EPMC6984131 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Early infantile epileptic-dyskinetic encephalopathy due to biallelic <i>PIGP</i> mutations.

Vetro Annalisa A Pisano Tiziana T Pisano Tiziana T Chiaro Silvia S Procopio Elena E Guerra Azzurra A Parrini Elena E Mei Davide D Virdò Simona S Mangone Giusi G Azzari Chiara C Guerrini Renzo R

Neurology. Genetics 20200102 1

<h4>Objective</h4>To describe clinical, biochemical, and molecular genetic findings in a large inbred family in which 4 children with a severe early-onset epileptic-dyskinetic encephalopathy, with suppression burst EEG, harbored homozygous mutations of phosphatidylinositol glycan anchor biosynthesis, class P (<i>PIGP</i>), a member of the large glycosylphosphatidylinositol (GPI) anchor biosynthesis gene family.<h4>Methods</h4>We studied clinical features, EEG, brain MRI scans, whole-exome sequen ...[more]

PMID: 32042915

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Dataset Information

Early infantile epileptic-dyskinetic encephalopathy due to biallelic PIGP mutations.

Publications

Early infantile epileptic-dyskinetic encephalopathy due to biallelic <i>PIGP</i> mutations.

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