TY - JOUR
T1 - 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
AU - Marangi, Giuseppe
AU - Di Giacomo, Marilena Carmela
AU - Lattante, Serena
AU - Orteschi, Daniela
AU - Doronzio, Paolo Niccolo'
AU - Riviello, Francesco Nicola
AU - Vaisfeld, Alessandro
AU - Frangella, Silvia
AU - Zollino, Marcella
PY - 2018
Y1 - 2018
N2 - KAT6B sequence variants have been identified in both patients with the SayâBarberâBieseckerâYoungâSimpson syndrome (SBBYSS) and in the genitopatellar syndrome (GPS). In SBBYSS, they were reported to affect mostly exons 16â18 of KAT6B, and the predicted mechanism of pathogenesis was haploinsufficiency or a partial loss of protein function. Truncating variants in KAT6B leading to GPS appear to cluster within the proximal portion of exon 18, associated with a dominant-negative effect of the mutated protein, most likely. Although SBBYSS and GPS have been initially considered allelic disorders with distinctive genetic and clinical features, there is evidence that they represent two ends of a spectrum of conditions referable as KAT6B-related disorders. We detected a de novo truncating variant within exon 7 of KAT6B in a 8-year-old female who presented with mild intellectual disability, facial dysmorphisms highly consistent with SBBYSS, and skeletal anomalies including exostosis, that are usually considered component manifestations of GPS. Following the clinical diagnosis driven by the striking facial phenotype, we analyzed the KAT6B gene by NGS techniques. The present report highlights the pivotal role of clinical genetics in avoiding clear-cut genotype-phenotype categories in syndromic forms of intellectual disability. In addition, it further supports the evidence that a continuum exists within the clinical spectrum of KAT6B-associated disorders.
AB - KAT6B sequence variants have been identified in both patients with the SayâBarberâBieseckerâYoungâSimpson syndrome (SBBYSS) and in the genitopatellar syndrome (GPS). In SBBYSS, they were reported to affect mostly exons 16â18 of KAT6B, and the predicted mechanism of pathogenesis was haploinsufficiency or a partial loss of protein function. Truncating variants in KAT6B leading to GPS appear to cluster within the proximal portion of exon 18, associated with a dominant-negative effect of the mutated protein, most likely. Although SBBYSS and GPS have been initially considered allelic disorders with distinctive genetic and clinical features, there is evidence that they represent two ends of a spectrum of conditions referable as KAT6B-related disorders. We detected a de novo truncating variant within exon 7 of KAT6B in a 8-year-old female who presented with mild intellectual disability, facial dysmorphisms highly consistent with SBBYSS, and skeletal anomalies including exostosis, that are usually considered component manifestations of GPS. Following the clinical diagnosis driven by the striking facial phenotype, we analyzed the KAT6B gene by NGS techniques. The present report highlights the pivotal role of clinical genetics in avoiding clear-cut genotype-phenotype categories in syndromic forms of intellectual disability. In addition, it further supports the evidence that a continuum exists within the clinical spectrum of KAT6B-associated disorders.
KW - focused exome sequencing
KW - kat6b
KW - focused exome sequencing
KW - kat6b
UR - http://hdl.handle.net/10807/111709
UR - http://onlinelibrary.wiley.com/journal/10.1002/(issn)1552-4833
U2 - 10.1002/ajmg.a.38571
DO - 10.1002/ajmg.a.38571
M3 - Article
SN - 1552-4825
VL - 176
SP - 455
EP - 459
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
ER -