Evidence of the milder phenotypic spectrum of c.1582G>A PIGT variant: Delineation based on seven novel Polish patients

Aleksandra Jezela-Stanek; Elżbieta Szczepanik; Hanna Mierzewska; Małgorzata Rydzanicz; Karolina Rutkowska; Alexej Knaus; Robert Śmigiel; Iwona Stępniak; Michał G Markiewicz; Snir Boniel; Peter Krawitz; Rafał Płoski

doi:10.1111/cge.13822

Evidence of the milder phenotypic spectrum of c.1582G>A PIGT variant: Delineation based on seven novel Polish patients

Clin Genet. 2020 Nov;98(5):468-476. doi: 10.1111/cge.13822.

Affiliations

¹ Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.
² Clinic of Pediatric Neurology, Institute of Mother and Child, Warsaw, Poland.
³ Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
⁴ Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
⁵ Department of Pediatrics, Division Pediatric Propedeutics and Rare Disorders, Wroclaw Medical University, Wroclaw, Poland.
⁶ Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
⁷ First Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.

PMID: 32725661
DOI: 10.1111/cge.13822

Abstract

PIGT is one of over 29 glycosylphosphatidylinositol biosynthesis defect genes. Mutations cause genetically determined disorders characterized mainly by epilepsy with fever-sensitivity, central hypotonia, psychomotor delay and congenital malformations. The disease is known as multiple congenital anomalies-hypotonia-seizures syndrome 3 (MCAHS3) or glycosylphosphatidylinositol biosynthesis defect-7. Twenty-eight cases have been reported until today. We present seven novel Polish patients, all harboring 1582G>A variant in a homozygous or compound heterozygous state which seems to cause a milder phenotype of the disease.

Keywords: PIGT gene; antiepileptic drugs; developmental encephalopathy with epilepsy; fever-associated epilepsy; glycosylphosphatidylinositol biosynthesis defects.

MeSH terms

Acyltransferases / genetics*
Child
Child, Preschool
Developmental Disabilities / complications
Developmental Disabilities / genetics
Developmental Disabilities / pathology
Epilepsy / complications
Epilepsy / genetics*
Epilepsy / pathology
Female
Flow Cytometry
Glycosylphosphatidylinositols / deficiency*
Glycosylphosphatidylinositols / genetics
Homozygote
Humans
Infant
Intellectual Disability / complications
Intellectual Disability / genetics*
Intellectual Disability / pathology
Male
Mutation / genetics
Nervous System Malformations / complications
Nervous System Malformations / genetics
Nervous System Malformations / pathology
Pedigree
Phenotype
Poland
Psychomotor Disorders / genetics*
Psychomotor Disorders / pathology
Seizures / complications
Seizures / genetics*
Seizures / pathology

Substances

Glycosylphosphatidylinositols
Acyltransferases
COOH-terminal signal transamidase

Supplementary concepts

Glycosylphosphatidylinositol deficiency