Novel KDM6A (UTX) mutations and a clinical and molecular review of the X‐linked Kabuki syndrome (KS2). (27th March 2014)

• Record Type: Journal Article
• Authors: Banka, S.; Lederer, D.; Benoit, V.; Jenkins, E.; Howard, E.; Bunstone, S.; Kerr, B.; McKee, S.; Lloyd, I.C.; Shears, D.; Stewart, H.; White, S.M.; Savarirayan, R.; Mancini, G.M.S.; Beysen, D.; Cohn, R.D.; Grisart, B.; Maystadt, I.; Donnai, D.
• Is Part Of: Clinical genetics. Volume 87:Number 3(2015:Mar.)
• Page Start: 252
• Page End: 258
• Publication Date: 2014-03-27
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12363
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12363-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="cge12363-para-0001">We describe seven patients with <italic>KDM6A</italic> (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 <italic>KDM6A</italic> mutations. Our work shows that similar to the commoner Type 1 Kabuki syndrome (KS1, MIM 147920) caused by <italic>KMT2D</italic> (previously called <italic>MLL2</italic>) 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 <italic>KDM6A</italic> 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 <italic>KDM6A</italic> mutation in some patients.</p> </abstract>