Deep-Phenotyping the Less Severe Spectrum of PIGT Deficiency and Linking the Gene to Myoclonic Atonic Seizures

• DOI: 10.3389/fgene.2021.663643
• Publication Date: 2021-05-11T17:11:16Z
• Authors: Allan Bayat; Manuela Pendziwiat; Ewa Obersztyn; Paula Goldenberg; Pia Zacher; Jan Henje Döring; Steffen Syrbe; Amber Begtrup; Artem Borovikov; Artem Sharkov; Aneta Karasińska; Maria Giżewska; Wendy Mitchell; Eva Morava; Rikke S. Møller; Guido Rubboli
• Keywords: Compound heterozygosity

The two aims of this study were (i) to describe and expand the phenotypic spectrum PIGT deficiency in affected individuals harboring c.1582G>A; p.Val528Met or c.1580A > G; p.Asn527Ser variant either homozygous compound heterozygous state, (ii) identify potential genotype-phenotype correlations any differences disease severity among with without variants. existing literature was searched A detailed assessment performed 25 (both novel previously published) We compared between these Twenty-four carried Val528Met one individual displayed Asn527Ser a state. Disease compatible that variant. While had focal epilepsy, profound developmental delay (DD), risk premature death, those variants moderate severe DD later onset epilepsy both generalized seizures. Individuals for generally became seizure-free on monotherapy antiepileptic drugs, other who pharmaco-resistant. Two patients diagnosed myoclonic-atonic seizures, single patient eyelid myoclonia. Our comprehensive analysis large cohort published broadens phenotypical shows are associated milder phenotype less outcome. data show is new candidate gene myoclonic atonic epilepsy. correlation will be useful future genetic counseling. Natural history studies mild PIGT- related disorder may shed light hitherto unknown aspects rare disorder.