title: De novo PIK3R2 variant causes polymicrogyria, corpus callosum hyperplasia and focal cortical dysplasia.
abstract: We report an 8-year-old boy with a complex cerebral malformation, intellectual disability, and complex partial seizures. Whole-exome sequencing revealed a yet unreported de novo variant in the PIK3R2 gene that was recently associated with megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome and bilateral perisylvian polymicrogyria (BPP). Our patient showed cerebral abnormalities (megalencephaly, perisylvian polymicrogyria, and mega corpus callosum) that were consistent with these conditions. Imaging also showed right temporal anomalies suggestive of cortical dysplasia. Until now, only three variants (c.1117G>A (p.(G373R)), c.1126A>G (p.(K376E)) and c.1202T>C (p.(L401P))) affecting the SH2 domain of the PIK3R2 protein have been reported in MPPH and BPP syndromes. In contrast to the variants reported so far, the patient described herein exhibits the c.1669G>C (p.(D557H)) variant that affects a highly conserved residue at the interface with the PI3K catalytic subunit α. The phenotypic spectrum associated with variants in this gene and its pathway are likely to continue to expand as more cases are identified.
authors: Department of Translational Medicine, Section of Pediatrics, Federico II University, Naples, Italy.
authors: Gaetano
authors: G
authors: Terrone
authors: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors: Norine
authors: N
authors: Voisin
authors: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.|Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.|Bioinformatics Section, King Abdullah International Medical Research Center (KAIMRC), Riyadh, Kingdom of Saudi Arabia.|King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia.
authors: Ali
authors: A
authors: Abdullah Alfaiz
authors: Department of Translational Medicine, Section of Pediatrics, Federico II University, Naples, Italy.
authors: Gerarda
authors: G
authors: Cappuccio
authors: Department of Translational Medicine, Section of Pediatrics, Federico II University, Naples, Italy.
authors: Giuseppina
authors: G
authors: Vitiello
authors: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.|Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
authors: Nicolas
authors: N
authors: Guex
authors: Department of Diagnostic Imaging, Neuroradiology Unit, Federico II University, Naples, Italy.
authors: Alessandra
authors: A
authors: D'Amico
authors: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
authors: A
authors: A
authors: James Barkovich
authors: Department of Translational Medicine, Section of Pediatrics, Federico II University, Naples, Italy.|Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy.
authors: Nicola
authors: N
authors: Brunetti-Pierri
authors: Department of Translational Medicine, Section of Pediatrics, Federico II University, Naples, Italy.
authors: Ennio
authors: E
authors: Del Giudice
authors: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors: Alexandre
authors: A
authors: Reymond
mesh_terms: D061085:Agenesis of Corpus Callosum / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D006801:Humans; D008297:Male; D054220:Malformations of Cortical Development / Q000175:diagnosis / Q000235:genetics*; D020125:Mutation, Missense; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000235:genetics*; D065706:Polymicrogyria / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome
chemical_list: D019869:Phosphatidylinositol 3-Kinases; C560566:phosphoinositol-3 kinase regulatory subunit 2, human