Malformations of cortical development
Gene: TP73
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 11:35 a.m. | Last Modified: 1 Feb 2023, 11:35 a.m.
Panel Version: 3.11
Comment on list classification: There is now sufficient evidence to promote this gene to Green at the next GMS panel review - at least 7 unrelated families with distinct variants and relevant phenotypes. Supported by some functional data.
TP73 is also now associated with a relevant phenotype in OMIM (MIM# 619466) but is not yet listed in G2P.Created: 21 Sep 2021, 2:09 p.m. | Last Modified: 21 Sep 2021, 2:09 p.m.
Panel Version: 3.1295
PMID: 34077761 (2021) - Further 7 individuals from 5 families identified with different homozygous variants in this gene. All affected individuals exhibited cortical malformations characterised by lissencephaly, central muscular hypotonia and moderate to severe cognitive dysfunction.Created: 21 Sep 2021, 2:06 p.m. | Last Modified: 21 Sep 2021, 2:06 p.m.
Panel Version: 3.1294
Comment on list classification: Rating Red as gene only distinguished due to multiple hits in same candidate gene - patients display discordant phenotype and DD only reported in one patient.Created: 27 Aug 2020, 3:06 p.m. | Last Modified: 27 Aug 2020, 3:06 p.m.
Panel Version: 3.272
PMID: 31130284 (2019) - Two individuals with homozygous variants in this gene identified as part of a large candidate gene discovery study. Phenotype in one patient included lissencephaly and hypotonia; while the other, a 19-month-old female, presented motor delay, speech delay, cleft lip and/or palate, cortical dysplasia, pachygyria, and strabismus.Created: 27 Aug 2020, 3:04 p.m. | Last Modified: 27 Aug 2020, 3:04 p.m.
Panel Version: 3.271
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Ciliary dyskinesia, primary, 47, and lissencephaly, OMIM:619466
Publications
New publication adds further evidence for gene-disease association, PMID 34077761:
- Seven individuals from five unrelated families homozygous for TP73 variants (includes 1x large deletion, 1x splice variant, 1x frameshift and 2x nonsense variants) and cortical malformations/ID
- In vitro ciliogenesis experiments demonstrated that epithelial cells from TP73 variant carriers had reduced number of ciliated cells and shortened cilia resulting in abnormal ciliary clearance of the airways compared to healthy controlsCreated: 7 Aug 2021, 7:29 a.m. | Last Modified: 7 Aug 2021, 7:29 a.m.
Panel Version: 3.1216
Two unrelated families, no functional data.
Sources: Expert listCreated: 1 Mar 2020, 8:45 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Intellectual disability; lissencephaly
Publications
Tag Q3_21_rating was removed from gene: TP73.
Source Expert Review Green was added to TP73. Source NHS GMS was added to TP73. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
gene: TP73 was added gene: TP73 was added to Malformations of cortical development. Sources: Expert list,Expert Review Amber Q3_21_rating tags were added to gene: TP73. Mode of inheritance for gene: TP73 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TP73 were set to 31130284; 34077761 Phenotypes for gene: TP73 were set to Ciliary dyskinesia, primary, 47, and lissencephaly, OMIM:619466