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Severe microcephaly

Gene: TCF4

Red List (low evidence)

TCF4 (transcription factor 4)
EnsemblGeneIds (GRCh38): ENSG00000196628
EnsemblGeneIds (GRCh37): ENSG00000196628
OMIM: 602272, Gene2Phenotype
TCF4 is in 9 panels

2 reviews

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: Promoting this gene from grey to red. After consultation with the Genomics England Clinical Team it was decided that patients with Pitt-Hopkins syndrome are more likely to be following a route for explanation of global developmental delay/intellectual disability than severe microcephaly.
Created: 30 Jun 2021, 11:59 a.m. | Last Modified: 30 Jun 2021, 11:59 a.m.
Panel Version: 2.210
Microcephaly listed as a feature of Pitt-Hopkins syndrome #610954 (AD) in OMIM.

PMID:18728071 - Zweier et al 2008 - analysed TCF4 in 117 patients with a phenotype suggestive of Pitt-Hopkins syndrome. 16 were found to have TCF4 variants. All had severe mental retardation. Microcephaly was observed in 9/16 but the degree is not stated.

PMID: 21671391 - Marangi et al 2011 - report 14 Pitt-Hopkins syndrome patients with TCF4 mutations; 2 patients had large 18q21.2 chromosome deletions involving TCF4, 11 patients had gene mutations and one had a balanced translocation involving the TCF4 locus. 2 are reported with a OFC at or below the 3rd percentile at birth, and 7/14 with postnatal microcephaly but the degree is not stated.

PMID: 29318938 - Goodspeed et al 2018 - reviewed 25 case reports and case series of Pitt-Hopkins Syndrome published in the literature from 2007 to 2016, and found 282 cases reported in total. Microcephaly was noted in 85/144 (59%) cases, but the severity is not discussed.

PMID:22934316 - GeneReviews entry.
Created: 26 May 2021, 9:18 p.m. | Last Modified: 26 May 2021, 9:18 p.m.
Panel Version: 2.185

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Pitt-Hopkins syndrome OMIM:610954

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Well established gene-disease association. Microcephaly reported in around 60%.
Sources: Expert list
Created: 4 Sep 2020, 1:58 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Pitt-Hopkins syndrome, MIM# 610954

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
Phenotypes
  • Pitt-Hopkins syndrome, OMIM:610954
OMIM
602272
Clinvar variants
Variants in TCF4
Penetrance
None
Publications
Panels with this gene

History Filter Activity

30 Jun 2021, Gel status: 1

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: tcf4 has been classified as Red List (Low Evidence).

26 May 2021, Gel status: 0

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TCF4 were changed from Pitt-Hopkins syndrome, MIM# 610954 to Pitt-Hopkins syndrome, OMIM:610954

26 May 2021, Gel status: 0

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: TCF4 were set to 18728071; 22934316

4 Sep 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: TCF4 was added gene: TCF4 was added to Severe microcephaly. Sources: Expert list Mode of inheritance for gene: TCF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TCF4 were set to 18728071; 22934316 Phenotypes for gene: TCF4 were set to Pitt-Hopkins syndrome, MIM# 610954 Review for gene: TCF4 was set to GREEN gene: TCF4 was marked as current diagnostic