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Skeletal dysplasia

Gene: HDAC4

Amber List (moderate evidence)

HDAC4 (histone deacetylase 4)
EnsemblGeneIds (GRCh38): ENSG00000068024
EnsemblGeneIds (GRCh37): ENSG00000068024
OMIM: 605314, Gene2Phenotype
HDAC4 is in 7 panels

4 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

I don't know

Brachydactylies (with extraskeletal manifestations) gp of SD. Brachydactyly MR syndrome is associated with a 2q37del. Only 2 cases with variants in the gene, but these have been reclassified as VUS on OMIM - haploinsufficiency associated with brachydactyly but not ID? amber/green? Note added by AW - HDAC4 yes. Listed in Bonafe (brachydactyly-MR). Seems good scientific basis to implicate HDAC4 in phenotype eg Jean-Marcais Am J Med Genet 14; Review on behalf of Tracy Lester/Andrew Wilkie
Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Albright hereditary osteodystrophy type 3; Albright hereditary osteodystrophy-like syndrome; Brachydactyly-intellectual disability; Del(2)(q37) 600430

Publications

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: After review with members of the GMS Musculoskeletal specialist test group and Genomics England Clinicians it was decided to rate the HDAC4 gene amber for SNVs, but to keep the region covering this gene green (ISCA-37394-Loss (2q37.3 terminal region (includes HDAC4) Loss))
Created: 3 Oct 2019, 9:38 a.m. | Last Modified: 3 Oct 2019, 9:40 a.m.
Panel Version: 1.203
Not associated with a phenotype in OMIM.
See review of this gene on Limb disorders panel - https://panelapp.genomicsengland.co.uk/panels/384/gene/HDAC4/
Conclusion was haploinsufficiency of HDAC4 appears to be associated with Brachydactyly type E but not always intellectual disability.
Created: 7 May 2019, 10:28 p.m.
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: HDAC4 (2q37del); Initial rating suggestion: I don't know
Created: 6 Mar 2019, 11:36 a.m.

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with phenotype in G2P. Numerous reports of haploinsufficiency suggest involvement of HDAC4 in skeletal dysplasia..
Created: 12 Jul 2016, 8:23 a.m.

Ana Beleza (Bristol Regional Genetics Service)

Green List (high evidence)

Tier 2
Created: 17 Jun 2016, 8:04 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Albright hereditary osteodystrophy type 3, Albright hereditary osteodystrophy-like syndrome, Brachydactyly-intellectual disability, Del(2)(q37) 600430

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 Amber
  • NHS GMS
  • Emory Genetics Laboratory
  • UKGTN
  • Expert list
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Albright hereditary osteodystrophy type 3
  • Brachydactyly-intellectual disability
  • Albright hereditary osteodystrophy type 3, Albright hereditary osteodystrophy-like syndrome, Brachydactyly-intellectual disability, Del(2)(q37) 600430
  • Albright hereditary osteodystrophy-like syndrome
  • Del(2)(q37) 600430
OMIM
605314
Clinvar variants
Variants in HDAC4
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

3 Oct 2019, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: hdac4 has been classified as Amber List (Moderate Evidence).

6 May 2019, Gel status: 4

Set Phenotypes, Set publications

Eleanor Williams (Genomics England Curator)

Added phenotypes Albright hereditary osteodystrophy type 3; Brachydactyly-intellectual disability; Albright hereditary osteodystrophy-like syndrome; Del(2)(q37) 600430 for gene: HDAC4 Publications for gene HDAC4 were changed from 20691407; 15521982; 19365831 to 19365831; 15521982; 20691407; 25402011

6 Mar 2019, Gel status: 3

Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to HDAC4. Rating Changed from Green List (high evidence) to Green List (high evidence)

9 Aug 2016, Gel status: 4

panel promoted to version 1

Sarah Leigh (Genomics England Curator)

Promoted to version 1 9th August 2016

12 Jul 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

12 Jul 2016, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for HDAC4 were set to Albright hereditary osteodystrophy type 3, Albright hereditary osteodystrophy-like syndrome, Brachydactyly-intellectual disability, Del(2)(q37) 600430

12 Jul 2016, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for HDAC4 were set to 20691407; 15521982; 19365831

12 Jul 2016, Gel status: 3

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for HDAC4 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

12 Jul 2016, Gel status: 3

Upload gene information

Sarah Leigh (Genomics England Curator)

HDAC4 was added to Unexplained skeletal dysplasiapanel. Sources: Emory Genetics Laboratory,Expert list,Radboud University Medical Center, Nijmegen,UKGTN

18 May 2016, Gel status: 0

Added New Source

Sarah Leigh (Genomics England Curator)

HDAC4 was added to Unexplained skeletal dysplasiapanel. Sources:

18 May 2016, Gel status: 0

Created

Sarah Leigh (Genomics England Curator)

HDAC4 was created by sleigh