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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 8 panels

3 reviews

Bryony Thompson (Royal Melbourne Hospital)

Green List (high evidence)

4 different missense present in the 14-3-3 binding site, identified de novo in 7 cases with an intellectual disability syndrome, and supporting in vitro functional assays
Created: 27 Nov 2020, 5:44 a.m. | Last Modified: 27 Nov 2020, 5:44 a.m.
Panel Version: 0.5474

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual disability; hypotonia; dysmorphism

Publications

Created: 27 Nov 2020, 5:44 a.m.
Last Modified: 27 Nov 2020, 5:44 a.m.
Panel version: Imported from Mendeliome panel version 0.7195

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Comment when marking as ready: Contradictory evidence: deletions linked to brachydactyly-MR but note some individuals reported without MR. Only two reports of intragenic variants (still structural rather than SNVs).
Created: 6 Feb 2020, 6 a.m. | Last Modified: 6 Feb 2020, 6:03 a.m.
Panel Version: 0.1271
Created: 6 Feb 2020, 6 a.m.
Last Modified: 6 Feb 2020, 6:03 a.m.
Panel version: Imported from Mendeliome panel version 0.1271

Elena Savva (Victorian Clinical Genetics Services)

I don't know

No OMIM phenotype. Chromosome multigenic 2q37 deletion commonly reported, SNVs in papers minimal.
ClinVar: 2 missense only, more reported in Decipher under DDD study.

Aspromente (2019) notes the disease association confirmation is pending

Williams (2010) reports haploinsufficiency as a mechanism. Notes NMD escape evidence - not shown
Wheeler (2014) mouse studies suggest GOF

Gene is amber for skeletal dysplasia (PanelApp UK), but genomic region is green
Created: 6 Feb 2020, 3:52 a.m. | Last Modified: 6 Feb 2020, 3:52 a.m.
Panel Version: 0.1262

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

Phenotypes
Brachydactyly mental retardation syndrome; Brachydactyly without intellectual disability

Publications

Mode of pathogenicity
Other

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

Created: 6 Feb 2020, 3:52 a.m.
Last Modified: 6 Feb 2020, 3:52 a.m.
Panel version: Imported from Mendeliome panel version 0.1262

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert Review Amber
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • NHS GMS
  • Expert list
  • Emory Genetics Laboratory
  • Victorian Clinical Genetics Services
Phenotypes
  • Albright hereditary osteodystrophy-like syndrome
  • Albright hereditary osteodystrophy type 3, Albright hereditary osteodystrophy-like syndrome, Brachydactyly-intellectual disability, Del(2)(q37) 600430
  • Albright hereditary osteodystrophy type 3
  • Brachydactyly-intellectual disability
  • Del(2)(q37) 600430
OMIM
605314
Clinvar variants
Variants in HDAC4
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Dec 2019, Gel status: 2

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

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: HDAC4 was added gene: HDAC4 was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory,Expert list,NHS GMS,Radboud University Medical Center, Nijmegen,UKGTN,Expert Review Amber Mode of inheritance for gene: HDAC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HDAC4 were set to 15521982; 25402011; 19365831; 20691407 Phenotypes for gene: HDAC4 were set to Albright hereditary osteodystrophy-like syndrome; Albright hereditary osteodystrophy type 3, Albright hereditary osteodystrophy-like syndrome, Brachydactyly-intellectual disability, Del(2)(q37) 600430; Albright hereditary osteodystrophy type 3; Brachydactyly-intellectual disability; Del(2)(q37) 600430