Novel CTR9 germline pathogenic splice site variant in siblings with Wilms tumor from Tanzania

Abstract

Wilms tumor is the most common childhood renal malignancy. Though mostly non-genetic, it can be syndromic with the involvement of many Wilms tumor predisposing genes and non-syndromic with the involvement of four genes: WT1, REST, TRIM28, and CTR9. Familial and bilateral Wilms tumors do occur, but these are rare. So far, four Wilms tumor families with pathogenic variants in the CTR9 gene have been described, all (presumably) inherited from unaffected fathers, and three leading to deletion of exon 9. We are reporting female siblings, of whom one has a bilateral Wilms tumor, with a novel pathogenic splice site variant in the CTR9 gene, leading to deletion of exon 9, and inherited from their asymptomatic father. The loss of heterozygosity in the tumor was confirmed. In conclusion, CTR9 pathogenic variants are a very rare cause of Wilms tumors and typically result in familial Wilms tumors.