De novo missense variants in PPP2R5D are associated with intellectual disability, macrocephaly, hypotonia, and autism

Original research article by L. Shang et al. (2016)

Read the abstract here.

Intellectual Disability (ID) and autism spectrum disorder (ASD) often have a genetic basis; however, identifying this genetic basis often poses a challenge to clinicians and researchers. With new developments in technology over the years, whole-exome sequencing (WES) has become a helpful method in identifying new gene changes associated with many different conditions.

WES was performed in 2,790 people with ID and/or developmental delay (DD). Of these 2,790 people, researchers identified seven with de novo changes (changes not found in either parent) in the PPP2R5D gene. The PPP2R5D gene is linked to a protein in the brain which plays an important role in signaling within the brain, neuron development, and regulation processes. Changes in this gene can have an effect on development.

The seven people identified with PPP2R5D changes ranged in age from 22 months to 15 years old. All seven had ID and/or DD, delays in walking and talking (with two people noted as being non-verbal), and low muscle tone (hypotonia). All but one person was diagnosed with ASD, and all but one person was observed as having macrocephaly (larger than typical head size). See the table below for additional clinical features observed. These findings support the idea the PPP2R5D gene is linked to ID and ASD.

Clinical Features Observed in 7 People with PPP2R5D Changes


Clinical Feature Number of Individuals with Feature
Intellectual Disability/Developmental Delay 7/7
Delayed walking 7/7
Delayed language/speech 7/7
Low IQ 4/7
Macrocephaly 6/7
Hypotonia 7/7
Autism Spectrum Disorder 6/7
Behavioral issues 4/7
Seizures 1/7
Differences in facial features 6/7
Brain abnormalities 4/7
Skeletal abnormalities 3/7
Ophthalmological abnormalities 5/7
Cardiac abnormalities 7/7