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Journal Articles European Journal of Human Genetics Year : 2015

Further delineation of the KAT6B molecular and phenotypic spectrum

1 Regional Genetic Service, St Mary's Hospital, Manchester
2 Clinical Genetics Service
3 Haukeland University Hospital
4 Royal Brsibane and Womens' Hospital, The University of Queensland
5 Department of Clinical Genetics
6 Service de génétique médicale
7 Institute of Human Genetics
8 Institute of Human Genetics - Institut für Humangenetik [Essen]
9 Karolinska University Hospital [Stockholm]
10 University Hospitals Bristol
11 University of Birmingham [Birmingham]
12 Hacettepe University Children's Hospital
13 Centre de Génétique Humaine, Institut de Pathologie et de Génétique
14 Division of Genetics, Birth Defects and Metabolism
15 Clinical Genetics
16 North West london hospitals NHS Trust
17 Department of Clinical Genetics, Northampton General Hospital, Northampton
18 Barzilai Medical Center
19 Cliniques Universitaires Saint-Luc [Bruxelles]
20 Service de génétique [Tours]
21 IGDR - Institut de Génétique et Développement de Rennes
22 Service de génétique clinique [Rennes]
23 Pediatrics
24 Clinical Genetics
25 University of Groningen [Groningen]
26 Belfast City Hospital
27 Centre For Medical Genetics
28 Clinical Genetic Service
29 Institute of Medical Genetics, Heath Park, Cardiff
30 National Centre for Medical Genetics
31 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico
32 Dipartimento di Medicina Molecolare
33 UZ Leuven - campus Gasthuisberg
34 East Anglian Medical Genetics Service, Cytogenetics Laboratory, Addenbrooke's Hospital
35 Department of Clinical Genetics
36 Service de Génétique
37 Clinical Genetics
38 Service de Génétique humaine
Mohnish Suri
  • Function : Author
  • PersonId : 888990
Julie Vogt
  • Function : Author
  • PersonId : 887726
Shehla Mohammed
  • Function : Author
  • PersonId : 922035
Annick Toutain
Beyhan Tuysuz
  • Function : Author
  • PersonId : 909534
Mark Tein
  • Function : Author
Willie Reardon
  • Function : Author
  • PersonId : 944062
Emilia Bijlsma
  • Function : Author
  • PersonId : 906916


KAT6B sequence variants have been identified previously in both patients with the Say-Barber-Biesecker type of blepharophimosis mental retardation syndromes (SBBS) and in the more severe genitopatellar syndrome (GPS). We report on the findings in a previously unreported group of 57 individuals with suggestive features of SBBS or GPS. Likely causative variants have been identified in 34/57 patients and were commonly located in the terminal exons of KAT6B. Of those where parental samples could be tested, all occurred de novo. Thirty out of thirty-four had truncating variants, one had a missense variant and the remaining three had the same synonymous change predicted to affect splicing. Variants in GPS tended to occur more proximally to those in SBBS patients, and genotype/phenotype analysis demonstrated significant clinical overlap between SBBS and GPS. The de novo synonymous change seen in three patients with features of SBBS occurred more proximally in exon 16. Statistical analysis of clinical features demonstrated that KAT6B variant-positive patients were more likely to display hypotonia, feeding difficulties, long thumbs/great toes and dental, thyroid and patella abnormalities than KAT6B variant-negative patients. The few reported patients with KAT6B haploinsufficiency had a much milder phenotype, though with some features overlapping those of SBBS. We report the findings in a previously unreported patient with a deletion of the KAT6B gene to further delineate the haploinsufficiency phenotype. The molecular mechanisms giving rise to the SBBS and GPS phenotypes are discussed.


Human genetics
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Dates and versions

hal-01195741 , version 1 (05-11-2015)



Tamsin Gannon, Rahat Perveen, Hélene Schlecht, Simon Ramsden, Beverley Anderson, et al.. Further delineation of the KAT6B molecular and phenotypic spectrum. European Journal of Human Genetics, 2015, 23 (9), pp.1165--1170. ⟨10.1038/ejhg.2014.248⟩. ⟨hal-01195741⟩
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