Mosaic brain disorders - deep sequencing

Gene: PIK3R2

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
OMIM:603387; Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

Publications

• PMID: 31441589

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Green List (high evidence)

Comment on classification: This gene should be rated GREEN as identified from multiple (>3) unrelated cases.

Megalencephaly (MEG) plus polymicrogyria (PMG) consistent with Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH) was reported in 12 unrelated children with two recurrent variants (11 with p.Gly373Arg and one with p.Lys376Glu). The key clinical features included severe MEG and PMG with mild or moderate ID and epilepsy (PMID:26520804). Two additional variants (p.Leu401Pro & p.Asp557His) have also been reported in one individual each from PMID:23745724 and PMID:26860062.

This gene-disease association has also been reported in OMIM.

Created: 21 Dec 2022, 3:48 p.m. | Last Modified: 21 Dec 2022, 3:48 p.m.

Panel Version: 0.32

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, 603387

Publications

• 23745724
• 26520804
• 26860062
• 31441589

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 5:26 p.m. | Last Modified: 1 Feb 2023, 5:29 p.m.

Panel Version: 0.93

Review submitted on behalf of Dr Lara Menzies, Dr Wendy Jones, Dr Amy McTague. Mode of inheritance: AD, can be post zygotic mosaic). Publications: Dobbyns and Mirzaa, AJMG 2019. Mechanism: Gain of function (MTOR Pathway). Penetrance: variable penetrance.

Created: 21 Dec 2022, 12:16 p.m. | Last Modified: 21 Dec 2022, 12:16 p.m.

Panel Version: 0.2

Phenotypes
MPPH (Megalencephaly polymicrogyria polydactyly hydrocephalus syndrome)

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments