ArticleJournal of dental research2018
Loss-of-Function GRHL3 Variants Detected in African Patients with Isolated Cleft Palate.
Article in Journal of dental research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 29 citations in OpenAlex.
- Rare variants in PRKCI cause Van der Woude syndrome and other features of peridermopathy.American journal of human genetics · 2025Article
- Loss of the epithelial transcription factor grhl3 leads to variably penetrant developmental phenotypes in zebrafish.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Functional Validation of Noncoding Variants Associated With Nonsyndromic Orofacial Cleft.Human mutation · 2025Review
- Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value.Journal of ovarian research · 2024Article
- A Comprehensive Genetic Analysis of Slovenian Families with Multiple Cases of Orofacial Clefts Reveals Novel Variants in the GenesInternational journal of molecular sciences · 2023Article
- Novel GRHL3 Variants in a South African Cohort With Cleft Lip and Palate.The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association · 2022Article
- Grainyhead-like (Grhl) Target Genes in Development and Cancer.International journal of molecular sciences · 2022Review
- Mouse models in palate development and orofacial cleft research: Understanding the crucial role and regulation of epithelial integrity in facial and palate morphogenesis.Current topics in developmental biology · 2022Article
- The genetic determinants of oral diseases in Africa: The gaps should be filled.Frontiers in oral health · 2022Review
- Identification of Novel Variants in Cleft Palate-Associated Genes in Brazilian Patients With Non-syndromic Cleft Palate Only.Frontiers in cell and developmental biology · 2021Article
- Article
- Spotlight on the Granules (Grainyhead-Like Proteins) - From an Evolutionary Conserved Controller of Epithelial Trait to Pioneering the Chromatin Landscape.Frontiers in molecular biosciences · 2020Review
- Functional Characterization of a Novel IRF6 Frameshift Mutation From a Van Der Woude Syndrome Family.Frontiers in genetics · 2020Article
- Three GLI2 mutations combined potentially underlie non-syndromic cleft lip with or without cleft palate in a Chinese pedigree.Molecular genetics & genomic medicine · 2019Article
- Wnt signaling in orofacial clefts: crosstalk, pathogenesis and models.Disease models & mechanisms · 2019Review
- Prospects of genetic testing for steroid-resistant nephrotic syndrome in Nigerian children: a narrative review of challenges and opportunities.International journal of nephrology and renovascular disease · 2019Review
- Medical genetics and genomic medicine in Nigeria.Molecular genetics & genomic medicine · 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
37 authors at 14 institutions in 7 countries.
Funding
Abstract
In contrast to the progress that has been made toward understanding the genetic etiology of cleft lip with or without cleft palate, relatively little is known about the genetic etiology for cleft palate only (CPO). A common coding variant of grainyhead like transcription factor 3 ( GRHL3) was recently shown to be associated with risk for CPO in Europeans. Mutations in this gene were also reported in families with Van der Woude syndrome. To identify rare mutations in GRHL3 that might explain the missing heritability for CPO, we sequenced GRHL3 in cases of CPO from Africa. We recruited participants from Ghana, Ethiopia, and Nigeria. This cohort included case-parent trios, cases and other family members, as well as controls. We sequenced exons of this gene in DNA from a total of 134 nonsyndromic cases. When possible, we sequenced them in parents to identify de novo mutations. Five novel mutations were identified: 2 missense (c.497C>A; p.Pro166His and c.1229A>G; p.Asp410Gly), 1 splice site (c.1282A>C p.Ser428Arg), 1 frameshift (c.470delC; p.Gly158Alafster55), and 1 nonsense (c.1677C>A; p.Tyr559Ter). These mutations were absent from 270 sequenced controls and from all public exome and whole genome databases, including the 1000 Genomes database (which includes data from Africa). However, 4 of the 5 mutations were present in unaffected mothers, indicating that their penetrance is incomplete. Interestingly, 1 mutation damaged a predicted sumoylation site, and another disrupted a predicted CK1 phosphorylation site. Overexpression assays in zebrafish and reporter assays in vitro indicated that 4 variants were functionally null or hypomorphic, while 1 was dominant negative. This study provides evidence that, as in Caucasian populations, mutations in GRHL3 contribute to the risk of nonsyndromic CPO in the African population.
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.