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Hearing loss

Gene: TSPEAR

Red List (low evidence)

TSPEAR (thrombospondin type laminin G domain and EAR repeats)
EnsemblGeneIds (GRCh38): ENSG00000175894
EnsemblGeneIds (GRCh37): ENSG00000175894
OMIM: 612920, Gene2Phenotype
TSPEAR is in 3 panels

3 reviews

Eleanor Williams (Genomics England Curator)

After review with the NHS GMS hearing specialist group on 2019-02-13 it was decided to keep this gene red. One case reported in Sloan-Heggen et al 2016 with variants associated with hearing loss. Variants reported in Delmaghani et al. (2012) have since been reported in individuals without hearing loss.
Created: 27 Feb 2019, 11:48 a.m.
TSPEAR is associated provisionally with ?Deafness, autosomal recessive 98 (614861) in OMIM (AR).

PMID: 22678063 - Delmaghani et al. (2012) - consanguineous Iranian family segregating autosomal recessive nonsyndromic sensorineural deafness (DFNB98; 614861), identified homozygosity for 2 adjacent variants in the TSPEAR gene (1726G>T and 1728delC) that segregated with deafness in the family. The deletion is predicted to create a frameshift in both the short and the long transcripts (p.V576LfsX37). These variants were absent from 152 unrelated normally hearing, Iranian individuals and from 200 normally hearing individuals living in France. Functional studies using wild type and mutant murine protein in V-5-tagged wild-type or mutant murine Tspear proteins in transfected HEK293 cells showed that both the wild-type and the mutant proteins were detected in the cell lysates, but only the wild-type form could be detected in the culture media, thus indicating defective secretion of the mutant protein. Transfection of COS-7 cells showed that the mutated Tspear was restricted to the endoplasmic reticulum but the wild-type Tspear was detected at the cell surface.

PMID: 27736875 - Peled et al. (2016) - found the same two variants as Delmaghani et al. in 2 female cousins from a consanguineous Arab Muslim family with ectodermal dysplasia-14, hair/tooth type with hypohidrosis. Both patients had NORMAL hearing by audiometric testing. Another unrelated patient was compound heterozygous for the 2 variants plus an additional 4-bp deletion. They had normal hearing but ectodermal dysplasia.

PMID: 26969326 - Sloan-Heggen et al 2016 - 1 patient with Autosomal recessive non-syndromic hearing loss with two heterozygous variants in TSPEAR - a deletion NM_001272037:c.1472_1473delAT and a silent substitution NM_001272037:c.1362G>A, p.Pro454Pro.
Created: 27 Feb 2019, 11:46 a.m.

Emma Ashton (Great Ormond Street Hospital)

I don't know

Sloan-Heggen et al 2016 PMID 26969326. Screened 1119 HL patients, 1 silent variant (said likely pathogenic as likely spl effect last base exon 9) 1 frameshift in one patient. Also frameshift reported by Delmaghani et al 2012 PMID 22678063, later reported by 2 other authors in patients with tooth agenesis not hearing loss.
Created: 17 Feb 2019, 4:35 p.m.

Publications

Jun Shen (Harvard Medical School)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#614861:Deafness, autosomal recessive 98[Sensorineural deafness, profoundNo auditory brainstem response to 100-dB stimulusTransient evoked otoacoustic emissions cannot be detected]

Publications

Details

Sources
  • Expert
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Deafness, autosomal recessive 98, 614861
OMIM
612920
Clinvar variants
Variants in TSPEAR
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

1 May 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: TSPEAR were set to

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

TSPEAR was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

TSPEAR was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Radboud University Medical Center, Nijmegen,Expert