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.
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Acknowledgements
Authors thank the family for its contribution and the members of the Lausanne Genomic Technologies Facility. AAA is recipient of a scholarship from the Saudi Arabian National Guard Health Affairs. This work was supported by a grant of the Swiss National Science Foundation 31003A_160203 and the Lithuanian-Swiss Cooperation Programme (AR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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During the revision of this manuscript, Mirzaa et al.5 reported PIK3R2 variants in BPP, we modified our manuscript to discuss our results in view of these recently published data to help potential readers getting a complete view of current knowledge.
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Terrone, G., Voisin, N., Abdullah Alfaiz, A. et al. De novo PIK3R2 variant causes polymicrogyria, corpus callosum hyperplasia and focal cortical dysplasia. Eur J Hum Genet 24, 1359–1362 (2016). https://doi.org/10.1038/ejhg.2016.7
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DOI: https://doi.org/10.1038/ejhg.2016.7
