Description: Genetically complex non-syndromic recessively inherited hearing loss (NSRHL) comprises approximately 75% of hereditary deafness. This study investigated NSRHL in two large consanguineous Pakistani families. Exome sequencing coupled with homozygosity mapping was used to identify a missense variant in PPIP5K2 gene associated with nonsyndromic, prelingual sensorineural deafness. Biochemical analysis was performed to compare wild type human PPIP5K2 with the variant. Additional research was conducted on mouse mutants to observe the effects on the outer hair cells and hearing thresholds. This dataset includes genetic, hearing function, gene expression, and histological data and images.
Geographic Coverage: Punjab (Pakistan)

Subject of Study

Subject Domain

Keywords

Access via Article
Access Restrictions: Unrestricted access
Access Instructions: All relevant data are within the paper and its supporting information files.
Associated Publications: Yousaf R, Gu C, Ahmed ZM, Khan SN, Friedman TB, Riazuddin S, et al. (2018) Mutations in Diphosphoinositol-Pentakisphosphate Kinase PPIP5K2 are associated with hearing loss in human and mouse. PLoS Genet 14(3): e1007297. https://doi.org/10.1371/journal.pgen.1007297
Data Type: Genetic

Histological

Gene Expression Analysis

Hearing Function

Genotype
Software Used: gEAR
Website for visualization and analysis of multiomic data both in public and private domains

NHLBI Exome Sequencing Project
Exome Variant Server

Primer3
PCR primer design tool

PrimeTime qPCR Primer Assays
Primer-only premixed assays for analyzing gene expression using intercalating dyes

SHIELD
Resource for dissemination and comparison of inner-ear gene expression datasets
Study Type: Empirical Research
Dataset Format(s): Microsoft Word, Chart, TIF, Chromatogram, Graph, Confocal Image

Grant Support: DC000039-20/National Institute on Deafness and Other Communication Disorders (NIDCD)

ES080046-28/National Institute of Environmental Health Sciences (NIEHS)

R56DC011803-07/National Institute on Deafness and Other Communication Disorders (NIDCD)

R01DC016295/National Institute on Deafness and Other Communication Disorders (NIDCD)
Other Resources: S1 Figure (TIF)
The DFNB100 locus on chromosome 5q13.2-q23.2

S2 Figure (TIF)
Anti-PPIP5K2 and anti-PPIP5K1 antibodies validations

S3 Figure (TIF)
Murine PPIP5K1 and PPIP5K2 have similar expression profiles

S4 Figure (TIF)
SDS-PAGE gel showing the purified recombinant PPIP5K2WT, PPIP5K2R837H and PPIP5K21-466 proteins used for functional studies

S5 Figure (TIF)
Representative ABR wave forms from control and mutant mice at various developmental stages

S6 Figure (TIF)
No obvious degeneration of spiral ganglion neurons or stria vascularis was observed in Ppip5k2+/K^ and Ppip5k2K^/K^ mice at P150

S1 Table (DOCX)
Whole exome sequencing filtration scheme

S2 Table (DOCX)
Bioinformatics evaluation of deafness-associated variants found in PPIP5K2

S3 Table (DOCX)
SNP genotypes in 1,885,410 bp flanking PPIP5K2 variant

S4 Table (DOCX)
Primer sequences used to amplify and sequence human PPIP5K2 coding exons and splice junctions

UMB Data Catalog

Mutations in Diphosphoinositol-Pentakisphosphate Kinase PPIP5K2 are associated with hearing loss in human and mouse
UMB Dataset