title: 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.
abstract: Genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) are two distinct clinically overlapping syndromes caused by de novo heterozygous truncating mutations in the KAT6B gene encoding lysine acetyltransferase 6B, a part of the histone H3 acetyltransferase complex. We describe an 8-year-old girl with a KAT6B mutation and a combined GPS/SBBYSS phenotype. The comparison of this patient with 61 previously published cases with KAT6B mutations and GPS, SBBYSS or combined GPS/SBBYSS phenotypes allowed us to separate the KAT6B mutations into four groups according to their position in the gene (reflecting nonsense mediated RNA decay and protein domains) and their clinical outcome. We suggest that mutations in mid-exon 18 corresponding to the C-terminal end of the acidic (Asp/Glu-rich) domain of KAT6B may have more variable expressivity leading to GPS, SBBYSS or combined phenotypes, in contrast to defects in other regions of the gene which contribute more specifically to either GPS or SBBYSS. Notwithstanding the clinical overlap, our cluster analysis of phenotypes of all known patients with KAT6B mutations supports the existence of two clinical entities, GPS and SBBYSS, as poles within the KAT6B-related disease spectrum. The awareness of these phenomena is important for qualified genetic counselling of patients with KAT6B mutations.
authors.affiliation: Department of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic. Electronic address: marketa.vlckova@lfmotol.cuni.cz.
authors.forename: Marketa
authors.initials: M
authors.lastname: Vlckova
authors.affiliation: Department of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Simandlova
authors.affiliation: Department of Statistics and Probability, Faculty of Informatics and Statistics, University of Economics, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Zimmermann
authors.affiliation: Institute of Inherited Metabolic Disorders, Charles University 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Viktor
authors.initials: V
authors.lastname: Stranecky
authors.affiliation: Institute of Inherited Metabolic Disorders, Charles University 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Hartmannova
authors.affiliation: Institute of Inherited Metabolic Disorders, Charles University 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Hodanova
authors.affiliation: Department of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Marketa
authors.initials: M
authors.lastname: Havlovicova
authors.affiliation: Department of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Hancarova
authors.affiliation: Institute of Inherited Metabolic Disorders, Charles University 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kmoch
authors.affiliation: Department of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Sedlacek
mesh_terms: D001483:Base Sequence; D016569:Blepharophimosis / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D003409:Congenital Hypothyroidism / Q000175:diagnosis / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005091:Exons; D019066:Facies; D005260:Female; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics*; D051548:Histone Acetyltransferases / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D007593:Joint Instability / Q000175:diagnosis / Q000235:genetics*; D007668:Kidney / Q000002:abnormalities*; D008969:Molecular Sequence Data; D009154:Mutation; D010329:Patella / Q000002:abnormalities*; D010641:Phenotype; D011596:Psychomotor Disorders / Q000175:diagnosis / Q000235:genetics*; D012611:Scrotum / Q000002:abnormalities*; D014564:Urogenital Abnormalities / Q000175:diagnosis / Q000235:genetics*
chemical_list: D051548:Histone Acetyltransferases; C487137:KAT6B protein, human
keywords: Genitopatellar syndrome; Genotype-phenotype correlation; KAT6B; Say-Barber-Biesecker-Young-Simpson syndrome