Intervento del Prof. Ennio Del Giudice alla riunione del NBG del 28 Aprile 2016
Patologia neurologica da mutazioni nel pathway PI3K-AKT-mTOR
Neurogenetic disorders due to mutations in the PI3K-AKT-mTOR pathway.
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 perisylvianpolymicrogyria (BPP). Our patient showed cerebral
abnormalities (megalencephaly, perisylvianpolymicrogyria, 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.
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 perisylvianpolymicrogyria (BPP). Our patient showed cerebral
abnormalities (megalencephaly, perisylvianpolymicrogyria, 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.
