These authors contributed equally to the paper.
Novel KDM6A (UTX) mutations and a clinical and molecular review of the X-linked Kabuki syndrome (KS2)
Article first published online: 27 MAR 2014
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
How to Cite
Novel KDM6A (UTX) mutations and a clinical and molecular review of the X-linked Kabuki syndrome (KS2)., , , , , , , , , , , , , , , , , , .
The authors declare no conflict of interest.
- Article first published online: 27 MAR 2014
- Accepted manuscript online: 14 FEB 2014 09:40AM EST
- Manuscript Revised: 12 FEB 2014
- Manuscript Accepted: 12 FEB 2014
- Manuscript Received: 2 JAN 2014
- Central Manchester University Hospitals NHS Foundation Trust. Grant Number: 629396
- Kabuki syndrome;
We describe seven patients with KDM6A (located on Xp11.3 and encodes UTX) mutations, a rare cause of Kabuki syndrome (KS2, MIM 300867) and report, for the first time, germ-line missense and splice-site mutations in the gene. We demonstrate that less than 5% cases of Kabuki syndrome are due to KDM6A mutations. Our work shows that similar to the commoner Type 1 Kabuki syndrome (KS1, MIM 147920) caused by KMT2D (previously called MLL2) mutations, KS2 patients are characterized by hypotonia and feeding difficulties during infancy and poor postnatal growth and short stature. Unlike KS1, developmental delay and learning disability are generally moderate–severe in boys but mild–moderate in girls with KS2. Some girls may have a normal developmental profile. Speech and cognition tend to be more severely affected than motor development. Increased susceptibility to infections, join laxity, heart, dental and ophthalmological anomalies are common. Hypoglycaemia is more common in KS2 than in KS1. Facial dysmorphism with KDM6A mutations is variable and diagnosis on facial gestalt alone may be difficult in some patients. Hypertrichosis, long halluces and large central incisors may be useful clues to an underlying KDM6A mutation in some patients.