Journal article
TSPEAR variants are primarily associated with ectodermal dysplasia and tooth agenesis but not hearing loss: A novel cohort study
American journal of medical genetics. Part A, Vol.185(8), pp.2417-2433
08/2021
DOI: 10.1002/ajmg.a.62347
PMCID: PMC8361973
PMID: 34042254
Abstract
Biallelic loss‐of‐function variants in the thrombospondin‐type laminin G domain and epilepsy‐associated repeats (TSPEAR) gene have recently been associated with ectodermal dysplasia and hearing loss. The first reports describing a TSPEAR disease association identified this gene is a cause of nonsyndromic hearing loss, but subsequent reports involving additional affected families have questioned this evidence and suggested a stronger association with ectodermal dysplasia. To clarify genotype–phenotype associations for TSPEAR variants, we characterized 13 individuals with biallelic TSPEAR variants. Individuals underwent either exome sequencing or panel‐based genetic testing. Nearly all of these newly reported individuals (11/13) have phenotypes that include tooth agenesis or ectodermal dysplasia, while three newly reported individuals have hearing loss. Of the individuals displaying hearing loss, all have additional variants in other hearing‐loss‐associated genes, specifically TMPRSS3, GJB2, and GJB6, that present competing candidates for their hearing loss phenotype. When presented alongside previous reports, the overall evidence supports the association of TSPEAR variants with ectodermal dysplasia and tooth agenesis features but creates significant doubt as to whether TSPEAR variants are a monogenic cause of hearing loss. Further functional evidence is needed to evaluate this phenotypic association.
Details
- Title: Subtitle
- TSPEAR variants are primarily associated with ectodermal dysplasia and tooth agenesis but not hearing loss: A novel cohort study
- Creators
- Bradley Bowles - Mayo ClinicAlejandro Ferrer - Mayo ClinicCarla J Nishimura - University of IowaFilippo Pinto e Vairo - Mayo ClinicTristan Rey - Université de StrasbourgBruno Leheup - Département de Médecine Infantile, CHRU de Nancy, Nancy, France.Jennifer Sullivan - Duke UniversityKelly Schoch - Duke UniversityNicholas Stong - Columbia UniversityEmanuele Agolini - Boston Children's HospitalDario Cocciadiferro - Boston Children's HospitalAbigail Williams - Boston Children's HospitalAlex Cummings - University of Wisconsin–MadisonSara Loddo - Boston Children's HospitalSilvia Genovese - Boston Children's HospitalChelsea Roadhouse - McMaster UniversityKirsty McWalter - GeneDxIngrid M Wentzensen - GeneDxChumei Li - McMaster UniversityDusica Babovic‐Vuksanovic - Mayo ClinicBrendan C Lanpher - Mayo ClinicMaria Lisa Dentici - Boston Children's HospitalArun Ankala - Emory UniversityJ. Austin Hamm - Boston Children's HospitalBruno Dallapiccola - Boston Children's HospitalFrancesca Clementina Radio - Boston Children's HospitalVandana Shashi - Duke UniversityBenedicte Gérard - Hôpitaux Universitaires de StrasbourgAgnes Bloch‐Zupan - Université de StrasbourgRichard J Smith - University of IowaUndiagnosed Diseases NetworkEric W Klee - Mayo Clinic
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part A, Vol.185(8), pp.2417-2433
- DOI
- 10.1002/ajmg.a.62347
- PMID
- 34042254
- PMCID
- PMC8361973
- NLM abbreviation
- Am J Med Genet A
- ISSN
- 1552-4825
- eISSN
- 1552-4833
- Publisher
- John Wiley & Sons, Inc
- Number of pages
- 17
- Grant note
- NIH Office of the Director (U01HG007672) National Science Foundation (NSF1744557) National Institute on Deafness and Other Communication Disorders (DC002842; DC012049)
- Language
- English
- Date published
- 08/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984256934602771
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