Submissions for variant NM_012330.4(KAT6B):c.4592del (p.Asn1531fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences	RCV003482189	SCV004227978	pathogenic	Genitopatellar syndrome; Blepharophimosis - intellectual disability syndrome, SBBYS type		criteria provided, single submitter	research	This truncating c.4592delA (p.Asn1531Thrfs*18) variant in the last KAT6B exon identified in our patient (a 4-year-old girl presenting with a serious multiple congenital anomaly syndrome) locates on the border between the SBBYSS/GTPTS mixed region and a pure SBBYSS region, in the middle of more than 100 amino acid ‘variant-desert’, where no other variants were described (PMID: 27452416). Clinical symptoms of our patient were clearly overlapping SBBYSS and GTPTS, suggesting equivocal clinical distinction between these disorders. Although five other patients with some overlapping phenotypes have also been described recently (PMID: 25424711, PMID: 26370006), neither of them overlap both SBBYSS and GTPTS to the degree observed in our patient. Our findings support that phenotypes associated with typical KAT6B disease-causing variants should be referred to as ‘KAT6B spectrum disorders’ or ‘KAT6B related disorders’, rather than their current SBBYSS and GTPTS classification.