Dominant mutations in KAT6A cause intellectual disability with recognizable syndromic features

Original research report by E. Tham et al. (2015)

Read the report here.

This article describes seven people from six unrelated families who were found to have genetic changes involving KAT6A. The main characteristics of these people are summarized in the table below.

Clinical Features Observed Number of Individuals with Feature
Global Developmental Delay/Intellectual Disability 7/7
Speech delay 7/7 (two use sign language)
Low muscle tone (hypotonia) 6/7
Skull abnormalities 6/7
Bitemporal narrowing 7/7
Broad nasal tip 7/7
Large/low set/posteriorly rotated ears 3/7
Slow weight gain 7/7
Thin upper lip 7/7
Downturned corners of the mouth 5/7
Patent Ductus Arteriosus (PDA) defect 5/7
Atrial Septal Defect (ASD) 4/7
Patent Foramen Ovale (PFO) defect 1/7
Ventricle Septum Defect (VSD) 1/7
Feeding problems 5/7
Eye problems 6/7

 

Six of the seven people had “truncating” changes, which result in a shortened, incomplete protein. One person had a deletion of the entire KAT6A gene. This indicated that having only one working copy of the KAT6A gene can be associated with the medical and developmental features described above. All of the genetic changes were de novo (not present in either parent) and were predicted to be damaging.