KAT6B-related disorder in a patient with a novel frameshift variant (c.3925dup)

Abstract

Heterozygous pathogenic variants in the KAT6B gene, which encodes lysine acetyltransferase 6B, have been identified in patients with congenital rare disorders, including genitopatellar syndrome and Say-Barber-Biesecker-Young-Simpson syndrome. Herein, we report another Japanese patient with a KAT6B-related disorder and a novel de novo heterozygous variant in exon 18 of KAT6B [c.3925dup, p.(Glu1309fs*33)], providing further evidence that truncating variants in exon 17 and in the proximal region of exon 18 are associated with genitopatellar syndrome-like phenotypes.

Keywords: Neurodevelopmental disorders; Next-generation sequencing.

Fig. 1. Clinical and genetic presentations of our case.

a Cryptorchidism, b agenesis of the corpus callosum, and c radioulnar synostosis. d An electropherogram of the KAT6B gene in the proband generated by direct sequencing shows a heterozygous frameshift variant in exon 18 [c.3925dup, p.(Glu1309fs*33)].

Fig. 2. The structure of the C-terminal region of KAT6B and the position of the pathogenic variants associated with KAT6B-related disorders.

The black and white boxes on genomic DNA (gDNA) denote the coding regions of exons 16–18 and the untranslated region, respectively. The variants leading to GPS and SBBYSS phenotypes are shown in bold and underline, respectively. a Variants with mixed or overlapping phenotypes. b Variant in the present patient.