Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder

Original research article by A. Chaudhry et al. (2015)

Read the abstract here.

This article reviews the features and characteristics of 23 people from 16 families who were found to have genetic changes in PTCHD1. This gene has been associated with autism spectrum disorder (ASD), intellectual disability (ID), and subtle differences in physical features. The types of change reported in this paper include large deletions (sections missing) and truncating changes (shorter than expected – not completely missing) that affect PTCHD and other genes. The PTCHD1 gene is on the X chromosome (one of the sex chromosomes that determines whether a person is a boy or a girl). Since boys only have one X chromosome, they may be more significantly affected than girls. Girls have two X chromosomes which gives them some protection because they still have an unaffected (functional) PTCHD1 gene on the other X. Girls with the change tend to have very few symptoms (if any), while boys with the change may be significantly affected. Unlike other genetic conditions included in the Simons Searchlight research, the majority of PTCHD1 changes identified in this study were found to be inherited (21 inherited families out of 23), and two people were found to have changes not from either parent (de novo). People were noted to have low muscle tone (hypotonia), especially in the facial muscles as an infant, motor/balance issues, and behavior issues (ID or ASD) including attention deficit-hyperactivity disorder (ADHD). People presented with minor differences in facial features including a long, narrow face, tall forehead, puffy eyelids, and a thin upper lip. No differences in brain structure or history of seizures were reported. One female subject had diagnoses of speech delay and ASD. Additional research is still needed to better understand the effects of genetic changes in PTCHD1 in females.