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, 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., DDD study, Smith, Janine and Clayton-Smith, Jill (2015) Further delineation of the KAT6B molecular and phenotypic spectrum. European Journal of Human Genetics, 23 9: 1165-1170. doi:10.1038/ejhg.2014.248

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.
DDD study
Smith, Janine
Clayton-Smith, Jill
Title Further delineation of the KAT6B molecular and phenotypic spectrum
Journal name European Journal of Human Genetics   Check publisher's open access policy
ISSN 1476-5438
Publication date 2015-09-14
Year available 2015
Sub-type Article (original research)
DOI 10.1038/ejhg.2014.248
Open Access Status Not Open Access
Volume 23
Issue 9
Start page 1165
End page 1170
Total pages 6
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted 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.
Keyword Say-Barber-Biesecker syndrome
KAT6B sequence
Genitopatellar syndrome
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID HICF-1009-003
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
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