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Intellectual disability

Gene: SATB1

Amber List (moderate evidence)

SATB1 (SATB homeobox 1)
EnsemblGeneIds (GRCh38): ENSG00000182568
EnsemblGeneIds (GRCh37): ENSG00000182568
OMIM: 602075, Gene2Phenotype
SATB1 is in 2 panels

4 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is now enough evidence to promote this gene to Green at the next major review.
Created: 10 Feb 2021, 12:55 p.m. | Last Modified: 10 Feb 2021, 12:55 p.m.
Panel Version: 3.775
Currently not associated with any phenotype in OMIM (last edited: 30/09/2020) but has a 'confirmed' disease confidence rating for 'SATB1-related developmental disorder (monoallelic)' in Gene2Phenotype.

- Den Hoed et al. 2021 (PMID: 33513338) - Total of 42 individuals from 35 families with SATB1 variants (including previously reported cases) - 30 patients harboured 15 unique SATB1 missense variants, including three recurrent variants; 10 had premature protein truncating variants; and and 2 individuals carried a (partial) gene deletion. 28 variants occurred de novo, 3 were inherited from an affected parent, 5 resulted from suspected parental mosaicism (2 inherited from an unaffected parent indicating reduced penetrance), and unknown inheritance in remaining 4 variants.

Phenotypes include neurodevelopmental delay (35/36, 97%), intellectual disability (28/31, 90%), muscle tone abnormalities (abnormal tone 28/37, 76%; hypotonia 28/37, 76%; spasticity 10/36, 28%), epilepsy (22/36, 61%), facial dysmorphisms (24/36, 67%), and dental abnormalities (24/34, 71%).

Missense variants were associated with a more severe phenotype - for instance, 57% of individuals with a missense variant had severe/profound ID whereas this level of ID was not observed for any individuals with truncating variants.
Created: 10 Feb 2021, 12:54 p.m. | Last Modified: 10 Feb 2021, 12:54 p.m.
Panel Version: 3.774

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

Ivone Leong (Genomics England Curator)

Comment on list classification: Gene promoted from Red to Amber based on the provided evidence.
Created: 4 Dec 2020, 3:08 p.m. | Last Modified: 4 Dec 2020, 3:08 p.m.
Panel Version: 3.592

Zornitza Stark (Australian Genomics)

Green List (high evidence)

PMID: 33513338: 42 patients with SNVs. 28 de novo, 3 inherited from an affected parent.
Missense variants - more severe, profound ID
NMD PTCs - milder disease

Consider adding to epilepsy and ataxia panels.
Created: 1 Feb 2021, 10:38 a.m. | Last Modified: 1 Feb 2021, 10:39 a.m.
Panel Version: 3.749
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 12 de novo (2 frameshift, 7 missense, 1 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Created: 4 Nov 2020, 5:07 a.m. | Last Modified: 4 Nov 2020, 5:07 a.m.
Panel Version: 3.510

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder

Publications

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

Eleanor Williams (Genomics England Curator)

I don't know

Conference talk/abstract from ESHG 2020 - Mutation-specific pathophysiological mechanisms in a new SATB1-associated neurodevelopmental disorder - Den Hoed et al - report 26 individuals with SATB1 variants, 17 of which have missense variants and 9 have truncating variants. 21 of 26 variants (80%) were confirmed to be de novo in origin. Patients showed a broad phenotypic spectrum, including ID and/or neurodevelopmental delay, epilepsy, dental abnormalities and aspecific brain MRI findings. Additionally, patients with missense variants are more severely affected than those with truncating variants.
No peer reviewed publication was found in PubMed relating to these results so recommend Amber rating for now.
Sources: Other
Created: 7 Jun 2020, 1:09 p.m. | Last Modified: 7 Jun 2020, 1:10 p.m.
Panel Version: 3.83

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

Phenotypes
intellectual disability

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Other
Phenotypes
  • intellectual disability
  • developmental disorders
Tags
Q2_21_rating
OMIM
602075
Clinvar variants
Variants in SATB1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

10 Feb 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: SATB1 were set to 33057194

10 Feb 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: satb1 has been classified as Amber List (Moderate Evidence).

10 Feb 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: satb1 has been classified as Amber List (Moderate Evidence).

10 Feb 2021, Gel status: 2

Removed Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist was removed from gene: SATB1. Tag Q2_21_rating tag was added to gene: SATB1.

4 Dec 2020, Gel status: 2

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: SATB1 were changed from intellectual disability to intellectual disability; developmental disorders

4 Dec 2020, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: satb1 has been classified as Amber List (Moderate Evidence).

4 Dec 2020, Gel status: 1

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: SATB1 were set to

23 Jun 2020, Gel status: 1

Added Tag

Eleanor Williams (Genomics England Curator)

Tag watchlist tag was added to gene: SATB1.

7 Jun 2020, Gel status: 1

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

Eleanor Williams (Genomics England Curator)

gene: SATB1 was added gene: SATB1 was added to Intellectual disability. Sources: Other Mode of inheritance for gene: SATB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SATB1 were set to intellectual disability Review for gene: SATB1 was set to AMBER