Diseases and pathogenesis of ATP6V1B2 gene mutations / 国际儿科学杂志

ABSTRACT

Mutations of ATP6V1B2(ATPase H + transporting V1 subunit B2)gene may cause dominant hereditary deafness and onychodystrophy(DDOD, MIM124480)syndrome and Zimmermann-Laband syndrome 2(ZLS2, MIM616455). It is demonstrated that patients with DDOD syndrome have learning or memory problems as well as congenital sensorineural hearing loss and nail aplasia or hypoplasia.ZLS2 is mainly characterized by gingival hypertrophy, hypo/aplastic nails and intellectual disability.Individuals are reported to have intellectual disability, epilepsy and milder ZLS2-type characteristics if they carry the variants clustering towards the middle of the ATP6V1B2 protein.ATP6V1B2 gene encodes B2 subunit of the multimeric vacuolar H + ATPase(V-ATPase), which is a proton pump responsible for controlling the intracellular and extracellular pH of cells and organelles.Research on Atp6v1b2 c. 1516C> T knockin mice showed that homozygous mice displayed obvious cognitive defects and impaired hippocampal CA1 region.A weak interaction between the E and B2 subunits might be the molecular mechanism underlyingV-ATPases dysfunction.It is of great significance to analyze and compare the phenotype caused by pathogenic mutations of ATP6V1B2 gene and to carry out functional research.