ArticleHuman genetics2013
A hypofunctional PAX1 mutation causes autosomal recessively inherited otofaciocervical syndrome.
Article in Human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Genome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci.Human molecular genetics · 2018Pooled it
- Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology.PLoS genetics · 2016Pooled it
- Review
- PAX1 represses canonical Wnt signaling pathway and plays dual roles during endoderm differentiation.Cell communication and signaling : CCS · 2024Article
- Review
- A Novel Truncating Mutation in PAX1 Gene Causes Otofaciocervical Syndrome Without Immunodeficiency.Journal of molecular neuroscience : MN · 2023Article
- Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients.Clinical immunology (Orlando, Fla.) · 2023Article
- Auricular fistula: a review of its clinical manifestations, genetics, and treatments.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Clinical Practice Guidelines for the Immunological Management of Chromosome 22q11.2 Deletion Syndrome and Other Defects in Thymic Development.Journal of clinical immunology · 2023Review
- Extending the PAX1 spectrum: a dominantly inherited variant causes oculo-auriculo-vertebral syndrome.European journal of human genetics : EJHG · 2022Article
- Clinical, Immunological, and Genetic Findings in a Cohort of Patients with the DiGeorge Phenotype without 22q11.2 Deletion.Journal of clinical medicine · 2022Article
- Developmental disorders caused by haploinsufficiency of transcriptional regulators: a perspective based on cell fate determination.Biology open · 2022Article
- An overview of PAX1: Expression, function and regulation in development and diseases.Frontiers in cell and developmental biology · 2022Review
- Novel genetic associations with five aesthetic facial traits: A genome-wide association study in the Chinese population.Frontiers in genetics · 2022Article
- The effects ofFASEB bioAdvances · 2021Article
- Article
- The Ever-Increasing Array of Novel Inborn Errors of Immunity: an Interim Update by the IUIS Committee.Journal of clinical immunology · 2021Review
- The application value of PAX1 and ZNF582 gene methylation in high grade intraepithelial lesion and cervical cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- Updates on new monogenic inborn errors of immunity.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2020Article
- A review of genetics of nasal development and morphological variation.Journal of family medicine and primary care · 2020Review
Corrections and comments
- Erratum issuedOnay, Melis Palamar [corrected to Palamar, Melis]
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Otofaciocervical syndrome (OFCS) is an autosomal recessively inherited disorder characterized by facial dysmorphism, external ear anomalies with preauricular pits and hearing impairment, branchial cysts or fistulas, anomalies of the vertebrae and the shoulder girdle, and mild intellectual disability. In a large consanguineous family with OFCS from Turkey, we performed whole-exome sequencing (WES) of a single pooled DNA sample of four affected individuals. Filtering for variants with a percentage of alternate reads ≥ 90 % and a coverage of at least five reads identified only a single novel homozygous variant, c.497G>T, located in PAX1 that co-segregated with the disease in the family. PAX1 encodes a transcription factor with a critical role in pattern formation during embryogenesis in vertebrates. The mutation is predicted to substitute the glycine at position 166 to valine (p.G166V) within the highly conserved paired-box domain of the PAX1 protein. We performed a dual luciferase reporter assay to examine the transactivation of a regulatory sequence in the Nkx3-2 promoter region, which is a direct target of mouse Pax1 transcriptional regulation. We observed a significantly reduced transactivation in HEK293T cells overexpressing Pax1(G157V) in comparison to Pax1(WT) expressing cells, indicating a reduced DNA-binding affinity of the mutant protein. Taken together, our results show that the strategy of pooling DNA is a powerful, cost-effective application for WES in consanguineous families and establish PAX1 as a new disease-causing gene for OFCS and as part of the EYA-DACH-SIX-PAX network, important in early embryogenesis.
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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.