Identifying the KAT6B Mutation via Diagnostic Exome Sequencing to Diagnose Say-Barber-Biesecker-Young-Simpson Syndrome in Three Generations of a Family

Abstract

Diagnostic exome sequencing (DES) is a powerful tool to analyze the pathogenic variants leading to development delay (DD) and intellectual disability (ID). Recently, heterozygous de novo mutation of the histone acetyltransferase encoding gene KAT6B has been recognized as causing a syndrome with congenital anomalies and intellectual disability, namely Say-Barber-Biesecker-Young-Simpson (SBBYS) syndrome. Here we report a case of SBBYS syndrome in a third generation Korean family affected with a missense mutation in KAT6B, c.2292C>T p.(His767Tyr) identified by DES. This is the first confirmed familial inherited mutation of the KAT6B reported worldwide. Our case emphasizes again the importance of basic physical examination and taking a family history. Furthermore, advances in genetic diagnostic tools are becoming key to identifying the etiology of DD and ID. This allows a physiatrist to predict the disease's clinical evolution with relative certainty, and offer an appropriate rehabilitation plan for patients.

The many lives of KATs — detectors, integrators and modulators of the cellular environment

“…In cases in which a given abnormality has not been detected or reported, its occurrence was taken as zero. Data were collated from reFs 136,137,139,142,144,147,149,[270][271][272][273] . RBS, Robert syndrome; RTS, Rubinstein-Taybi syndrome.…”

A neonate with Say–Barber–Biesecker–Young–Simpson syndrome with a novel pathogenic mutation in KAT6B gene: A case report

“…While KAT6B disorders are inherited in an autosomal dominant manner, most individuals with a KAT6B disorder have had a de novo pathogenic variant including ours. Kim et al [16] reported the familial inherited mutation of the KAT6B variant (c.2292C>T, p.His767Tyr) causing relatively mild disease in three individuals with SBBYSS. In Korea, two cases have reported KAT6B mutation including GPS (NM_012330.3: c4543C>T, p.Gln1515Ter) and familial SBBYSS mentioned above [16,17].…”

“…Kim et al [16] reported the familial inherited mutation of the KAT6B variant (c.2292C>T, p.His767Tyr) causing relatively mild disease in three individuals with SBBYSS. In Korea, two cases have reported KAT6B mutation including GPS (NM_012330.3: c4543C>T, p.Gln1515Ter) and familial SBBYSS mentioned above [16,17].…”

Delineation of a Phenotype Caused by a <b><i>KAT6B</i></b> Missense Variant Not Resembling Say-Barber-Biesecker-Young-Simpson and Genitopatellar Syndromes

“…Although causative variants of SBBYSS are located distally to exon 18 of KAT6B, those of GPS are located more proximally to exon 18 [Zhang et al, 2020]. Recently, several reports have shown that KAT6B variants in exons more proximal to exon 18 can cause unique SBBYSS and GPS phenotypes [Clayton-Smith et al, 2011;Kim et al, 2017;Marangi et al, 2018;Zhang et al, 2020]. Here, we present a patient with global developmental delay, intellectual disability, autistic behavior, muscular hypotonia, facial dysmorphism, and seizures, but with a phenotype different from that of SBBYSS and GPS caused by a de novo heterozygous missense variant in exon 7 of KAT6B.…”