ArticleAmerican journal of human genetics2016
Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- A new mutation of Sgms1 causes gradual hearing loss associated with a reduced endocochlear potential.Hearing research · 2024Article
- Autosomal recessive non-syndromic hearing loss genes in Pakistan during the previous three decades.Journal of cellular and molecular medicine · 2024Review
- Accurate phenotypic classification and exome sequencing allow identification of novel genes and variants associated with adult-onset hearing loss.PLoS genetics · 2023Article
- Mutations in human DNA methyltransferase DNMT1 induce specific genome-wide epigenomic and transcriptomic changes in neurodevelopment.Human molecular genetics · 2023Article
- Regionalized Protein Localization Domains in the Zebrafish Hair Cell Kinocilium.Journal of developmental biology · 2023Article
- Slit-Robo signalling establishes a Sphingosine-1-phosphate gradient to polarise fin mesenchyme.EMBO reports · 2022Article
- Identification of autosomal recessive nonsyndromic hearing impairment genes through the study of consanguineous and non-consanguineous families: past, present, and future.Human genetics · 2022Review
- Structure of S1PR2-heterotrimeric GScience advances · 2022Article
- G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss.Frontiers in molecular neuroscience · 2022Review
- Translational and interdisciplinary insights into presbyacusis: A multidimensional disease.Hearing research · 2021Review
- Homozygous mutations in Pakistani consanguineous families with prelingual nonsyndromic hearing loss.Molecular biology reports · 2020Article
- Small fish, big prospects: using zebrafish to unravel the mechanisms of hereditary hearing loss.Hearing research · 2020Article
- Post-translational modifications of S1PR1 and endothelial barrier regulation.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- Growth factor and receptor malfunctions associated with human genetic deafness.Clinical genetics · 2020Review
- Sphingosine 1-phosphate: Lipid signaling in pathology and therapy.Science (New York, N.Y.) · 2019Review
- Article
- Genetic Hearing Loss and Gene Therapy.Genomics & informatics · 2018Article
- The conserved p.Arg108 residue in S1PR2 (DFNB68) is fundamental for proper hearing: evidence from a consanguineous Iranian family.BMC medical genetics · 2018Article
- Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction.Human genetics · 2018Article
- Whole genome sequencing of Caribbean Hispanic families with late-onset Alzheimer's disease.Annals of clinical and translational neurology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 12 institutions in 3 countries.
Funding
Abstract
The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal-recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among ∼120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2(-/-) mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss were observed. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2(-/-) mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.