De novo nonsense mutations in KAT6A, a lysine acetyl-transferase gene, cause a syndrome including microcephaly and global developmental delay

Original research article by V.A. Arboleda et al. (2015)

Read the abstract here.

This article examines the effects of nonsense changes (genetic changes that result in a shortened, incomplete protein) in KAT6A that were identified in four unrelated people with developmental delay, small head size, and differences in facial features. Whole-exome sequencing showed that all four people had genetic changes not found in either parent. Three of the people were found to have the identical genetic change. The study provides evidence that changes of KAT6A are a cause of developmental delay. The common clinical features identified in these people are summarized in the table below.

Clinical Features Observed Number of Individuals with Feature
Small head size (microcephaly) 3/4
Developmental Delay (gross motor) 4/4
Intellectual Disability 4/4
Sleep disturbances 2/4
Differences in facial features 4/4
Cleft palate 1/4
Dental irregularities 2/4
Misalignment of eyes (strabismus) 3/4
Drooping eyelid (ptosis) 2/4
Difficulty seeing far (myopia) 1/4
Heart defects Atrial Septal Defect (ASD): 2/4, Ventricular Septal Defect (VSD): 1/4, Not examined: 1/4
Weakness or collapse of the windpipe 1/4
Chronic lung disease 2/4
GERD (Gastroesophageal Reflux Disease) 2/4
Feeding difficulty 3/4
Abnormal development of intestine (malrotation) 1/4
Excess fluid in kidney (hydronephrosis) 1/4
Undescended testicles (cryptorchidism) 1/4
Low muscle tone (hypotonia) 3/4
Short fingers/toes (brachydactyly) 2/4
Repetitive involuntary muscle movements (dystonia) 2/4