Correction: KAT6A Syndrome: genotype–phenotype correlation in 76 patients with pathogenic KAT6A variants

Abstract

The original version of this Article did not include Tatjana Bierhals, Maja Hempel, Jessika Johannsen, and Davor Lessel in the list of authors for their contribution to data collection and analysis. This has now been corrected in both the PDF and HTML versions of the Article.

Prenatal diagnosis of KAT6A syndrome in two fetuses with congenital heart disease

“…At 16 weeks, cardiac findings were confirmed and trio ES was performed, which revealed a heterozygous de-novo mutation, c.4663A > G (p.Ser1555Gly), in exon 17 of the KAT6A gene, which fulfilled the ACMG criteria PS2, PM1, PM2, PP3 and BP1-Class 4 and was classified as likely pathogenic 2 . Kennedy et al reported a similar variant, p.Ser1555Arg, in a cohort of 76 cases with Arboleda-Tham syndrome 3 . Subsequent examination at 18 + 5 weeks confirmed the cardiac findings in addition to bilateral pyelectasis and a head shape suggestive of brachycephaly with early signs of possible craniosynostosis (Figure 2b).…”

“…This analysis showed a de-novo heterozygous deletion of exons 13-17 within the KAT6A gene, which was classified as pathogenic as per the joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) 2 . The classification was assigned based on the deletion of multiple exons in a loss-of-function-intolerant gene, absence of similar deletions in population databases, previous reporting of multiple loss-of-function variants in the deleted region in patients with KAT6A syndrome 3 and the de-novo occurrence. The specific codes applied were 2E (PVS1_vs), 3A and 4C.…”

“…According to https://kat6a .org, there are 334 registered individuals with KAT6A syndrome at the time of writing and, to the best of our knowledge, our two cases are the first to be reported prenatally. Cardiac anomalies have been reported in up to 70% of patients with KAT6A syndrome, some of whom require surgery 3 . Patients have been reported to have an abnormal head shape, including microcephaly, brachycephaly and craniosynostosis [3][4][5][6] , as observed in our cases.…”

“…Cardiac anomalies have been reported in up to 70% of patients with KAT6A syndrome, some of whom require surgery 3 . Patients have been reported to have an abnormal head shape, including microcephaly, brachycephaly and craniosynostosis [3][4][5][6] , as observed in our cases. Of special interest is Case 1, in which the phenotypic features resembled a 22q11 deletion; it has been reported that KAT6A regulates expression of the TBX1 gene, leading to this similarity 7,8 .…”

“…Of special interest is Case 1, in which the phenotypic features resembled a 22q11 deletion; it has been reported that KAT6A regulates expression of the TBX1 gene, leading to this similarity 7,8 . Most cases in the literature were diagnosed using ES in individuals with an intellectual disability rather than a cardiac anomaly 3 . From a prenatal point of view, even with ultrasound findings of mild CHD, as in our cases, ES can be of benefit to families in addition to QF-PCR and CMA and is more likely to identify a diagnosis than is a small gene panel.…”