Genes in panel
STRs in panel
Prev Next
Regions in panel
Prev Next

Limb disorders

Gene: HDAC4

Green List (high evidence)

HDAC4 (histone deacetylase 4)
EnsemblGeneIds (GRCh38): ENSG00000068024
EnsemblGeneIds (GRCh37): ENSG00000068024
OMIM: 605314, Gene2Phenotype
HDAC4 is in 6 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Variants previously reported in OMIM in association with BRACHYDACTYLY-MENTAL RETARDATION SYNDROME are now reclassified as VUS following reports of Villavicencio-Lorini et al. (2013)(PMID:23188045) and Wheeler et al. (2014)(PMID:24715439).

Williams et al (2010)(PMID: 20691407) refined the BDMR critical region to a single gene, HDAC4. 2 unrelated cases of patients with no CNV covering HDAC4, but with SNVs in HDAC4 (c.2399_2400insC leading to p.Gly801TrpfsX77 and c.490+56_121del65 probably altering splicing of exons 5–6 ) and BDMR features including Brachydactyly type E in both patients.

Villavicencio-Lorini et al. 2013 (PMID: 23188045) report a family with a deletion covering the HDAC4, FLJ43879, and TWIST2 genes and presenting with very mild developmental delay and dysmorphic facial features but no brachydactyly. The conclusion was that HDAC4 haploinsufficiency is not fully penetrant for brachydactyly type E.

Ogura et al. (2014)(PMID: 25329715) heterozygous 3.2-Mb deletion that included the HDAC4 gene and did have brachydactyly type E.

Wheeler et al. (2014)(PMID: 24715439) reported a mother and 2 sons with a heterozygous 887-kb deletion including the entire coding region of the HDAC4 gene, 2 noncoding RNA sequences (MGC16025 and LOC150935), and 4 microRNAs. None of the individuals had intellectual disability, but the mother and the older son had type E brachydactyly.

Jean-Marçais et al (2015)(PMID: 25402011) - family with deletion covering HDAC4 and TWIST2. Patients presented with BDE and short stature without intellectual disability.

In conclusion, haploinsufficiency of HDAC4 appears to be associated with Brachydactyly type E but not always intellectual disability.
Created: 9 Dec 2018, 10:17 p.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
  • Emory Genetics Laboratory
  • Expert list
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
  • London South East RGC GSTT
  • Viapath
Phenotypes
  • Albright hereditary osteodystrophy type 3, Albright hereditary osteodystrophy-like syndrome, Brachydactyly-intellectual disability, Del(2)(q37) 600430
OMIM
605314
Clinvar variants
Variants in HDAC4
Penetrance
None
Publications
Panels with this gene

History Filter Activity

11 Dec 2018, Gel status: 4

Panel promoted to version 1.0

Eleanor Williams (Genomics England Curator)

Ana Beleza: Tier 2

5 Apr 2018, Gel status: 4

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

Ellen McDonagh (Genomics England Curator)

Expert Review Green was added to HDAC4. Panel: Limb disorders UKGTN was added to HDAC4. Panel: Limb disorders Radboud University Medical Center, Nijmegen was added to HDAC4. Panel: Limb disorders Expert list was added to HDAC4. Panel: Limb disorders Emory Genetics Laboratory was added to HDAC4. Panel: Limb disorders Model of inheritance for gene HDAC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene HDAC4 was set to ['20691407', '15521982', '19365831']

27 Nov 2017, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

London South East RGC GSTT was added to HDAC4. Panel: Limb disorders

17 Nov 2017, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

HDAC4 was added to Limb disorders panel. Sources: Viapath

17 Nov 2017, Gel status: 1

Created

Ellen McDonagh (Genomics England Curator)

HDAC4 was created by Ellen McDonagh