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Relevance to Autism

De novo likely-gene disruptive (LGD) variants in the PHF21A gene have been observed in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014) and in a proband with intellectual disability (Lelieveld et al., 2016). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified PHF21A as a gene with an excess of LGD variants (false discovery rata < 5%, count >1) (Coe et al., 2018). De novo translocations disrupting the PHF21A gene, as well as de novo truncating variants in PHF21A, have been identified in patients presenting with intellectual disability and dysmorphic facial features (Kim et al., 2012; Hamanaka et al., 2018). Potocki-Shaffer syndrome (OMIM 601224) is a contiguous gene deletion syndrome characterized by craniofacial abnormalities, developmental delay, intellectual disability, multiple exostoses, and biparietal foramina; autistic behavior has also been reported to associate with this syndrome (Swarr et al., 2010). Potocki-Shaffer syndrome involves genes on chromosome 11p11.2, and PHF21A has been proposed as a candidate gene responsible for at least some of the phenotypes observed in affected individuals.

Molecular Function

The PHF21A gene encodes BHC80, a component of a BRAF35 (MIM 605535)/histone deacetylase (HDAC; see MIM 601241) complex (BHC) that mediates repression of neuron-specific genes through the cis-regulatory element known as repressor element-1 (RE1) or neural restrictive silencer (NRS) in non-neuronal cells.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The contribution of de novo coding mutations to autism spectrum disorder.
ASD
Support
De novo truncating variants in PHF21A cause intellectual disability and craniofacial anomalies.
ID
Epilepsy/seizures, autistic features
Support
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability.
ID
Support
Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies.
ID
Support
Potocki-Shaffer syndrome: comprehensive clinical assessment, review of the literature, and proposals for medical management.
Potocki-Shaffer syndrome
ASD
Recent Recommendation
Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN1070R001 
 frameshift_variant 
  
  
 De novo 
  
 Simplex 
 GEN1070R002 
 frameshift_variant 
 c.1956del 
 p.Ala653fs 
 De novo 
  
 Simplex 
 GEN1070R003 
 translocation 
  
  
 De novo 
  
 Simplex 
 GEN1070R004 
 translocation 
  
  
 De novo 
  
 Simplex 
 GEN1070R005 
 translocation 
  
  
 De novo 
  
  
 GEN1070R006 
 frameshift_variant 
 c.1220dupC 
 p.Glu408ArgfsTer3 
 De novo 
  
 Simplex 
 GEN1070R007 
 stop_gained 
 c.1738C>T 
 p.Arg580Ter 
 De novo 
  
 Simplex 
 GEN1070R008 
 frameshift_variant 
 c.657_658insAA 
 p.Pro220AsnfsTer48 
 De novo 
  
 Simplex 

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
11
Deletion-Duplication
 15
 
11
Duplication
 1
 
11
Deletion
 2
 
11
Deletion
 2
 

No Animal Model Data Available

 

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