Bilateral congenital or childhood onset cataracts

Gene: KAT2B

I don't know

Comment on list classification: Setting the rating as red, as only 1 case with cataracts and only KAT2B has been reported.

Created: 5 Nov 2024, 2:33 p.m. | Last Modified: 5 Nov 2024, 2:33 p.m.

Panel Version: 6.3

1 case with homozygous variants in KAT2B with 2 siblings treated for bilateral cataracts in early childhood, along with a renal phenotype which develops later in childhood. An additional case where 3 siblings had bilateral cataracts either from birth or in early childhood but were an additional potentially pathogenic variant was found in the ADD gene.

PMID: 39366742 - Niel et al 2024 - 2 siblings originating from Montenegro who presented in teenage years with steroid-resistant nephrotic syndrome and had bilateral cataracts in early childhood. WES identified a homozygous variant in KAT2B in both patients (NM_003884.5:c.700dup, NP_003875.3:p.(Ser234LysfsTer13)), leading to a 1-base insertion, a frameshift and a premature stop codon in exon 6/18. The variant was not described in gnomAD, and was hetrozygous in both parents, who are unrelated but originate from the same geographical location in Montenegro. No pathogenic variants of other genes of interest, including ADD3 (previous cases with variants in both KAT2B and ADD and nephrotic syndrome have been reported PMID: 29768408), were identified.

PMID: 29768408 - Gonçalves et al 2018 - report 3 families with intellectual disability. Biallelic missense ADD variants were found in all probands, but in one family an additional homozygous variant (c.920T>C, p.F307S) was found in KAT2B. In this family, 3 affected siblings also presented with steroid-resistant nephrotic syndrome and proteinuira below the age of 13, dilated cardiomyopathy and bilateral cateracts. Bilateral cateracts were also reported in one of the probands with ADD variants only.
Sources: Literature

Created: 5 Nov 2024, 2:32 p.m. | Last Modified: 5 Nov 2024, 2:34 p.m.

Panel Version: 6.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
cataract, MONDO:0005129; Cataract, HP:0000518

Publications

• 39366742
• 29768408