title: De novoKAT6BMutation Identified with Whole-Exome Sequencing in a Girl with Say-Barber/Biesecker/Young-Simpson Syndrome.
abstract: Say-Barber/Biesecker/Young-Simpson syndrome (SBBYSS; OMIM 603736) is a rare syndrome with multiple congenital anomalies/malformations. The clinical diagnosis is usually based on a phenotype with a mask-like face and severe blepharophimosis and ptosis as well as other distinctive facial traits. We present a girl with dysmorphic features, an atrial septal defect, and developmental delay. Previous genetic testing (array-CGH, 22q11 deletion,PTPN11andMLL2mutation analysis) gave normal results. We performed whole-exome sequencing (WES) and identified a heterozygous nonsense mutation in theKAT6Bgene, NM_001256468.1: c.4943C>G (p.S1648*). The mutation led to a premature stop codon and occurred de novo.KAT6Bsequence variants have previously been identified in patients with SBBYSS, and the phenotype of the girl is similar to other patients diagnosed with SBBYSS. This case report provides additional evidence for the correlation between theKAT6Bmutation and SBBYSS. If a patient is suspected of having a blepharophimosis syndrome or SBBYSS, we recommend sequencing theKAT6Bgene. This is a further example showing that WES can assist diagnosis.
authors.affiliation: Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Malene
authors.initials: M
authors.lastname: Lundsgaard
authors.affiliation: Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Vang Q
authors.initials: VQ
authors.lastname: Le
authors.affiliation: Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Anja
authors.initials: A
authors.lastname: Ernst
authors.affiliation: Department of Paediatrics, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Laugaard-Jacobsen
authors.affiliation: Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Rasmussen
authors.affiliation: Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Inge S
authors.initials: IS
authors.lastname: Pedersen
authors.affiliation: Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Petersen
keywords: Blepharophimosis; Developmental delay; Epicanthus inversus; KAT6B; Ohdo syndrome; Whole-exome sequencing; Young-Simpson syndrome