Further delineation of the KAT6B molecular and phenotypic spectrum.
Simsek-Kiper, Pelin Ozlem
Van den Ende, Jenneke
Luk, Ho Ming
Pilz, Daniela T
Veenstra-Knol, Hermine E
Lo, Ivan F M
DNA Mutational Analysis
Genetic Association Studies
Heart Defects, Congenital
Severity of Illness Index
MetadataShow full item record
CitationFurther delineation of the KAT6B molecular and phenotypic spectrum. 2015, 23 (9):1165-70 Eur. J. Hum. Genet.
PublisherNature Publishing Group
JournalEuropean journal of human genetics : EJHG
AbstractKAT6B 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.
- De Novo Mutation of KAT6B Gene Causing Atypical Say-Barber-Biesecker-Young-Simpson Syndrome or Genitopatellar Syndrome.
- Authors: Li G, Li N, Li J, Ding Y, Yu T, Wang X, Wang J
- Issue date: 2017 Apr
- Complex phenotypes blur conventional borders between Say-Barber-Biesecker-Young-Simpson syndrome and genitopatellar syndrome.
- Authors: Radvanszky J, Hyblova M, Durovcikova D, Hikkelova M, Fiedler E, Kadasi L, Turna J, Minarik G, Szemes T
- Issue date: 2017 Feb
- A patient showing features of both SBBYSS and GPS supports the concept of a KAT6B-related disease spectrum, with mutations in mid-exon 18 possibly leading to combined phenotypes.
- Authors: Vlckova M, Simandlova M, Zimmermann P, Stranecky V, Hartmannova H, Hodanova K, Havlovicova M, Hancarova M, Kmoch S, Sedlacek Z
- Issue date: 2015 Oct
- A novel truncating variant within exon 7 of KAT6B associated with features of both Say-Barber-Bieseker-Young-Simpson syndrome and genitopatellar syndrome: Further evidence of a continuum in the clinical spectrum of KAT6B-related disorders.
- Authors: Marangi G, Di Giacomo MC, Lattante S, Orteschi D, Patrizi S, Doronzio PN, Riviello FN, Vaisfeld A, Frangella S, Zollino M
- Issue date: 2018 Feb
- A Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome with a KAT6B 10-base pair palindromic duplication: A recurrent mutation causing a severe phenotype mixed with genitopatellar syndrome.
- Authors: Niida Y, Mitani Y, Kuroda M, Yokoi A, Nakagawa H, Kato A
- Issue date: 2017 May