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Further delineation of the KAT6B molecular and phenotypic spectrum.

Gannon, Tamsin
; 
Perveen, Rahat
; 
Schlecht, Hélene
; 
Ramsden, Simon
; 
Anderson, Beverley
; 
Kerr, Bronwyn
; 
Day, Ruth
; 
Banka, Siddharth
; 
Suri, Mohnish
; 
Berland, Siren
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Author
Gannon, Tamsin
 Perveen, Rahat
 Schlecht, Hélene
 Ramsden, Simon
 Anderson, Beverley
 Kerr, Bronwyn
 Day, Ruth
 Banka, Siddharth
 Suri, Mohnish
 Berland, Siren
 Gabbett, Michael
 Ma, Alan
 Lyonnet, Stan
 Cormier-Daire, Valerie
 Yilmaz, Rüstem
 Borck, Guntram
 Wieczorek, Dagmar
 Anderlid, Britt-Marie
 Smithson, Sarah
 Vogt, Julie
 Moore-Barton, Heather
 Simsek-Kiper, Pelin Ozlem
 Maystadt, Isabelle
 Destrée, Anne
 Bucher, Jessica
 Angle, Brad
 Mohammed, Shehla
 Wakeling, Emma
 Price, Sue
 Singer, Amihood
 Sznajer, Yves
 Toutain, Annick
 Haye, Damien
 Newbury-Ecob, Ruth
 Fradin, Melanie
 McGaughran, Julie
 Tuysuz, Beyhan
 Tein, Mark
 Bouman, Katelijne
 Dabir, Tabib
 Van den Ende, Jenneke
 Luk, Ho Ming
 Pilz, Daniela T
 Eason, Jacqueline
 Davies, Sally
 Reardon, Willie
 Garavelli, Livia
 Zuffardi, Orsetta
 Devriendt, Koen
 Armstrong, Ruth
 Johnson, Diana
 Doco-Fenzy, Martine
 Bijlsma, Emilia
 Unger, Sheila
 Veenstra-Knol, Hermine E
 Kohlhase, Jürgen
 Lo, Ivan F M
 Smith, Janine
 Clayton-Smith, Jill
Advisors
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Other Contributors
Departments
Date
2015-09
Date Submitted
Keywords
GENETICS
INTELLECTUAL DISABILITIES
DEVELOPMENTAL DISABILITIES
Other Subjects
Subject Mesh
Blepharophimosis
Child, Preschool
Congenital Hypothyroidism
Craniofacial Abnormalities
DNA Mutational Analysis
Diagnosis, Differential
Exome
Exons
Facies
Female
Gene Expression
Genetic Association Studies
Genotype
Heart Defects, Congenital
Histone Acetyltransferases
Humans
Intellectual Disability
Joint Instability
Kidney
Male
Mutation
Patella
Phenotype
Psychomotor Disorders
Scrotum
Severity of Illness Index
Urogenital Abnormalities
Planned Date
Start Date
Collaborators
Principal Investigators
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Alternative Titles
Publisher
Nature Publishing Group
URI
https://hdl.handle.net/10147/620599
Abstract
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.
Language
en
Citation
Further delineation of the KAT6B molecular and phenotypic spectrum. 2015, 23 (9):1165-70 Eur. J. Hum. Genet.
ISSN
1476-5438
eISSN
ISBN
DOI
10.1038/ejhg.2014.248
PMID
25424711
PMCID
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