A novel homozygous in-frame deletion variant in TPRKB causing Galloway-Mowat syndrome 5.

Biallelic variants in TPRKB (TP53RK-binding protein) are known to cause Galloway–Mowat syndrome 5 (MIM#617731). It is a rare renal-neurologic disease characterized by early-onset nephrotic syndrome, facial dysmorphism, developmental delay, cerebral and cerebellar atrophy, and central nervous system white matter abnormalities. To date, four families with biallelic variants in TPRKB have been reported. We report two individuals from two unrelated families presenting with Galloway–Mowat Syndrome 5. Whole exome sequencing revealed a novel homozygous in-frame deletion, c.92_94del p.(Arg31del) in exon 2 of TPRKB (NM_016058.5) in both. In silico analysis of the TPRKB mutant protein showed alteration in the interactions with the neighboring residues due to Arg31 deletion, thus leading to altered protein conformation compared to the wild-type protein. Additionally, TPRKB mRNA levels were significantly reduced in the skin fibroblasts of proband 1. In addition, the phenotypic characteristics among GAMOS subtypes were reviewed.