Mosaic brain disorders - deep sequencing

Gene: PTPN11

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: 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 Jun 2023, 2:25 p.m. | Last Modified: 1 Jun 2023, 2:25 p.m.

Panel Version: 0.130

PMID:35687047 reported two cases with Focal cortical dysplasia type III (1 case each with FCDIIIa and FCDIIId) and identified with somatic variant in PTPN11 gene.

PMID:36864519 reported a patient with FCD type I and identified with somatic variant in PTPN11.

PMID:37126322 reported two cases with mesial temporal sclerosis (MTS) and identified with somatic variants in PTPN11 gene. In addition, it also reported another case presenting with MTS and low-grade epilepsy–associated tumors (LEAT) and with PTPN11 somatic variant.

PTPN11 has also been implicated in LEAT. A patient identified with somatic variant and presenting with LEAT was reported in PMID:36226386.

PMID:29257282 reported that the knockout of PTPN11 from radial glia in mice resulted in cerebral cortical dysplasia, glial defects of cerebellum and impaired sensory‑motor development in newborn mice, though epileptic activity and hippocampal pathology were not assessed.

Created: 1 Jun 2023, 2:16 p.m. | Last Modified: 1 Jun 2023, 2:18 p.m.

Panel Version: 0.126

Phenotypes
Focal cortical dysplasia; Mesial temporal sclerosis

Publications

• 29257282
• 35687047
• 36864519
• 36907520
• 37126322

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
FCD type 1, FCDIII

Publications

• 36864519
• PMID: 36635388

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