ClinGen Dosage Sensitivity Curation Page

TECTA

  • Curation Status: Complete

Location Information

  • 11q23.3
  • GRCh37/hg19 chr11: 120,973,375-121,061,515
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr11: 121,102,666-121,190,806
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000011.9) (NC_000011.10)
Evidence for haploinsufficiency phenotype
PubMed ID Description
12746400 Naz et al. 2003 identified 2 families with segregation of nonsyndromic deafness. One family had the c.649dup (p.Thr217AsnfsX32, stop in exon 5) variant and the other family had the c.6037delG (p.Glu2013ArgfsX6, stop in exon 20/23) variant. The c.649dup family had 10 affecteds and 8 unaffecteds and the c.6037delG had 3 affecteds and 5 unaffecteds. These variants are both predicted to cause truncated or absent protein leading to loss of function (LOF) and haploinsufficiency. Therefore, their detection and segregation in individuals with deafness provides support for haploinsufficiency as the mechanism for autosomal recessive deafness 21.
28012541 Asgharzade et al. 2017 identified a consanguineous Iranian family with prelingual moderate to severe sensorineural hearing loss that was more severe at mid frequencies. Through linkage analysis and then TECTA sequencing, they identified a novel c.734G>A (p.W245X) variant in exon 5 of TECTA that segregated with disease in 5 affected and 2 unaffected individuals. This variant is also a convincing loss of function (LOF) variant that provides support for AR LOF leading to prelingual hearing loss that is usually profound but in this case was moderate to severe.
21520338 This study identified a c.1124delT p.Val375AlaX4 variant that was found to segregate in an autosomal dominant manner in a Spanish family. This supports that haploinsufficiency is a mechanism instead of just biallelic LOF. This study did only sequence exons and flanking intronic regions of TECTA so they may still be considered coincidental carriers for a mutation that is not detectable by the methods used in the study.

Haploinsufficiency phenotype comments:

There have been at least 8 cases of autosomal recessive deafness caused by biallelic loss of function of TECTA. Though the phenotype is traditionaly thought of as profound deafness, many families experienced moderate to severe stable or mid frequency hearing loss. Though the phenotypic spectrum is somewhat broad, the mechanism of autosomal recessive loss of function is definitely established by case data.Of note, Hildebrand et al. identified a frameshift variant that segregated in an autosomal dominant manner with postlingual mid frequency hearing loss. This study did only sequence exons and flanking intronic regions of TECTA so they may still be considered coincidental carriers for a mutation that is not detectable by the methods used in the study. Variation in TECTA has been reported in individuals with ADNSHL and ARNSHL. Furthermore, the overall evidence that TECTA, when altered, can cause ADNSHL or ARNSHL was expert reviewed by the ClinGen Hearing Loss Working Group and classified as DEFINITIVE

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

There is currently no distinct phenotype for TECTA triplosensitivity.