TSPEAR variants are primarily associated with ectodermal dysplasia and tooth agenesis but not hearing loss: A novel cohort study.
TSPEAR
autosomal recessive deafness
ectodermal dysplasia
hearing loss
tooth agenesis
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
12
04
2021
received:
21
10
2020
accepted:
22
04
2021
pubmed:
28
5
2021
medline:
13
1
2022
entrez:
27
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34042254
doi: 10.1002/ajmg.a.62347
pmc: PMC8361973
doi:
Substances chimiques
Proteins
0
TSPEAR protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2417-2433Subventions
Organisme : NHGRI NIH HHS
ID : U01 HG007672
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC012049
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC002842
Pays : United States
Informations de copyright
© 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
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