ATP6V1B2-related epileptic encephalopathy

Epileptic Disord. 2020 Jun 1;22(3):317-322. doi: 10.1684/epd.2020.1166.

Abstract

ATP6V1B2 encodes a subunit of the lysosomal transmembrane proton pump necessary for adequate functioning of several acid hydrolases. De novo monoallelic variants of this gene have been associated with two distinct phenotypes: Zimmermann-Laband syndrome 2 (ZLS2), an intellectual deficiency/multiple malformation syndrome, and dominant deafness onychodystrophy (DDOD), a multiple malformation syndrome without cognitive involvement. Epilepsy is not observed in DDOD, is variably present in ZLS2, but is a common feature in Zimmermann-Laband syndrome 1 (ZLS1) (caused by monoallelic pathogenic variants in KCNH1) and Zimmermann-Laband syndrome-like (ZLSL) (associated with KCNK4 variants). Herein, we report a case of an infant with severe epileptic encephalopathy with microcephaly and profound developmental delay, associated with a novel de novo loss-of-function variant in ATP6V1B2, diagnosed by whole-exome sequencing. This finding expands the spectrum of ATP6V1B2-associated disorders and adds ATP6V1B2 as a new member for the growing list of early-onset epileptic encephalopathy genes. [Published with video sequence].

Keywords: ATP6V1B2; Zimmermann-Laband syndrome 1; Zimmermann-Laband syndrome 2; dominant deafness onychodystrophy; epilepsy; epileptic encephalopathy.

Publication types

  • Case Reports

MeSH terms

  • Developmental Disabilities / genetics*
  • Epilepsy / genetics*
  • Humans
  • Infant, Newborn
  • Microcephaly / genetics*
  • Syndrome
  • Vacuolar Proton-Translocating ATPases / genetics*
  • Whole Exome Sequencing

Substances

  • Vacuolar Proton-Translocating ATPases
  • ATP6V1B2 protein, human