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

TY - JOUR

T1 - A novel homozygous in-frame deletion variant in TPRKB causing Galloway-Mowat syndrome 5

AU - Kaur, Namanpreet

AU - Shirsat, Khushbu

AU - Bhat, Vivekananda

AU - Yeole, Mayuri

AU - Farooqui, Sheeba

AU - Limaye, Sanket

AU - Radhakrishnan, Periyasamy

AU - Siddiqui, Shahyan

AU - Narayanan, Dhanya Lakshmi

AU - Shenoy, Rathika

AU - Shukla, Anju

N1 - Publisher Copyright: © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2026.

PY - 2026/2/14

Y1 - 2026/2/14

N2 - 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.

AB - 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.

KW - Galloway-Mowat syndrome 5

KW - In-frame deletion

KW - Microcephaly

KW - TPRKB

UR - https://www.scopus.com/pages/publications/105030166662

U2 - 10.1007/s10048-026-00884-5

DO - 10.1007/s10048-026-00884-5

M3 - Article

C2 - 41689604

AN - SCOPUS:105030166662

SN - 1364-6745

VL - 27

JO - Neurogenetics

JF - Neurogenetics

IS - 1

M1 - 15

ER -