HGNC Approved Gene Symbol: TECTA
Cytogenetic location: 11q23.3 Genomic coordinates (GRCh38): 11:121,101,243-121,191,490 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 11q23.3 | Deafness, autosomal dominant 8/12 | 601543 | Autosomal dominant | 3 |
| Deafness, autosomal recessive 21 | 603629 | Autosomal recessive | 3 |
The TECTA gene encodes alpha-tectorin, one of the major noncollagenous components of the tectorial membrane in the inner ear. The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals (Legan et al., 1997). See also TECTB (602653).
Legan et al. (1997) cloned the mouse alpha- and beta-tectorins. The mouse alpha-tectorin gene encodes a 2,150-amino acid protein with a hydrophobic secretory signal sequence and 33 potential N-glycosylation sites. The first 219 amino acids show 24.9% similarity to a region of entactin (NID; 131390), a basement membrane protein. The central domain contains several repeats of the 'D' domain found in prepro-von Willebrand factor (613160), zonadhesin (602372), and the intestinal mucin MUC2 (158370). The C terminus contains a zona pellucida domain, which is the only structural feature shared by alpha- and beta-tectorins.
Verhoeven et al. (1998) determined that the TECTA gene encodes a precursor protein of 2,155 amino acids with 95% identity to the mouse protein. Alpha-tectorin is proteolytically processed into 3 polypeptides: an entactin-homologous module, a zonadhesin-homologous module, and a zona pellucida module. There 3 polypeptides are crosslinked to each other by disulfide bridges and interact with beta-tectorin to form the noncollagenous matrix of the tectorial membrane.
Verhoeven et al. (1998) determined that the TECTA gene contains 23 exons.
Hughes et al. (1998) mapped the mouse Tecta gene to a region of chromosome 9 that shows evolutionary conservation with human chromosome 11q.
Autosomal Dominant Deafness 12
In 2 families with autosomal dominant nonsyndromic deafness-12 (DFNA12; 601543), Verhoeven et al. (1998) identified mutations in the TECTA gene (602574.0001; 602574.0002). One of the families had been designated DFNA8. Both mutations occurred in the zona pellucida domain and are predicted to disrupt the interactions between the different tectorin polypeptides, which would disrupt the structure of the tectorial membrane and lead to inefficient transmission of sound to the stereociliary bundle of the hair cells. This would be a dominant-negative effect.
Balciuniene et al. (1998) studied a Swedish kindred with autosomal dominant nonsyndromic hearing impairment with possible digenic inheritance of the disease, involving DFNA12 on chromosome 11 and DFNA2 (600101) on 1p35.1. Molecular analysis of this family by Balciuniene et al. (1999) identified a pathogenic mutation in the TECTA gene (C1057S; 602574.0004) in 9 severely affected members. The authors also identified 7 additional nucleotide substitutions, indicating that TECTA is highly polymorphic. Balciuniene et al. (1999) noted that the phenotype in the Swedish family differed from that reported in other families with TECTA mutations. The Swedish family showed progressive hearing loss with a later onset around age 9 years. The explanation for the different phenotypes may lie in the localization of the mutations in different modules of the protein. Another possibility is that the phenotype in the Swedish family resulted from 2 defective genes.
Autosomal Recessive Deafness 21
In affected members of a consanguineous Lebanese family with prelingual severe to profound sensorineural nonsyndromic deafness (DFNB21; 603629), Mustapha et al. (1999) identified a homozygous mutation in the TECTA gene (602574.0003). The findings established that alpha-tectorin mutations can be responsible for either dominant or recessive forms of deafness. Comparison of the phenotype of the DFNB21 heterozygous carriers with that of DFNA12-affected individuals suggested to Mustapha et al. (1999) that TECTA mutations causing the dominant form of deafness have a dominant-negative effect. These results provided genetic evidence that alpha-tectorin forms homeo- or heteromeric structures.
In affected members from 2 consanguineous families with hearing impairment (DFNB21), 1 from Iran and 1 from Pakistan, Naz et al. (2003) identified homozygosity for a 649insC (602574.0006) and a 6037delG (602574.0007) mutation in the TECTA gene, respectively. The authors concluded that DFNB21 due to homozygosity for mutations in the TECTA gene is characterized by a distinctive flat to shallow U-shaped audiogram.
In 3 consanguineous Iranian families with autosomal recessive nonsyndromic hearing loss showing homozygosity by descent for the DFNB21 locus, Meyer et al. (2007) identified homozygosity for 3 different inactivating mutations in the TECTA gene, respectively. The authors noted that the truncating nature of the mutations was consistent with loss of function, making the Tecta knockout mouse a good model for the study of DFNB21-related deafness.
Associations Pending Confirmation
Hughes et al. (1998) suggested that the TECTA gene may be implicated in Jacobsen syndrome (147791), a contiguous gene disorder caused by segmental aneusomy for distal 11q. The typical features, though not always present, include mild to moderate psychomotor retardation, trigonocephaly, facial dysmorphism, cardiac defects, and thrombocytopenia. Hearing loss or abnormality was described as a characteristic feature of Jacobsen syndrome by Lee and Sciorra (1981), although the overall frequency was not clear.
In a review of reported TECTA mutations, Iwasaki et al. (2002) suggested that mutations in the zona pellucida domain result in nonprogressive, mid-frequency prelingual hearing loss, whereas those in the zona adhesin domain result in progressive, high frequency hearing loss with onset in childhood.
Applying statistical analysis, Plantinga et al. (2006) found a significant association between TECTA mutations in the zona pellucida and zona adhesin domains and mid and high frequency hearing impairment, respectively. Cysteine-replacing mutations were associated with progressive hearing impairment.
Legan et al. (2000) found that Tecta-null mice had tectorial membranes that were detached from the cochlear epithelium and lacked all noncollagenous matrix. The architecture of the organ of Corti was otherwise normal. The basilar membranes of wildtype and alpha-tectorin mutant mice were tuned, but the alpha-tectorin mutants were 35-dB less sensitive. Basilar membrane responses of wildtype mice exhibited a second resonance, indicating that the tectorial membrane provides an inertial mass against which outer hair cells can exert forces. Cochlear microphonics recorded in alpha-tectorin mutants differed in both phase and symmetry relative to those of wildtype mice. The authors concluded that the tectorial membrane ensures that outer hair cells can effectively respond to basilar membrane motion and that feedback is delivered with the appropriate gain and timing required for amplification.
Legan et al. (2005) found that mice with a heterozygous mutation in the Tecta gene (Y1870C; 602574.0002) had a disrupted tectorial membrane with reduced thickness of the adhesion zone. However, sensory transduction by outer hair cells was not impaired, and the sensitivity and frequency tuning of the mechanical responses of the cochlea were little changed. Neural thresholds were elevated, neural tuning was broadened, and there was a decrease in sensitivity at the tip of the neural tuning curve. Legan et al. (2005) concluded that the findings implicated a second major role for the tectorial membrane in hearing: enabling the motion of the basilar membrane to optimally drive the inner hair cells at their best frequency.
In affected members of a Belgian family with autosomal dominant nonsyndromic deafness-12 (601543), Verhoeven et al. (1998) found heterozygosity for 2 mutations in exon 17 of the TECTA gene: a 5459C-T transition resulting in a leu1820-to-phe (L1820F) substitution, and a 5472G-A transition resulting in a gly1824-to-asp (G1824D) substitution. Eighteen affected members of the DFNA12 family had both mutations, but neither was present in any of the 40 unaffected family members or 100 controls. It was considered possible that one mutation could be a rare polymorphism, while the other is the disease-causing mutation. Alternatively, they might have a synergistic effect, neither being capable of producing disease by itself. The substitutions replaced conserved amino acid residues within the zona pellucida domain of TECTA. The hearing loss was prelingual and nonprogressive.
The nucleotide numbering of the mutations, originally given by Verhoeven et al. (1998) as 5725C-T and 5738G-A, was corrected in an erratum.
In an Austrian family with DFNA12 (601543), Verhoeven et al. (1998) found that affected members had a heterozygous 5610A-G transition in exon 18 of the TECTA gene, resulting in a tyr1870-to-cys (Y1870C) substitution within the zona pellucida domain. The deafness locus in this family had been designated DFNA8.
The nucleotide numbering of the mutation, originally given by Verhoeven et al. (1998) as 5876A-G, was corrected in an erratum.
In a Lebanese family presenting with a prelingual severe to profound sensorineural isolated form of deafness (603629), Mustapha et al. (1999) identified a G-to-A transition of the first nucleotide in the donor splice site of intron 9 of the TECTA gene, predicting a truncated protein of 971 amino acids. The mutation was homozygous in the 9 affected individuals and heterozygous in their parents. The mutation was predicted to lead to the skipping of exon 9, resulting in a premature stop codon at amino acid position 972. Based on the normal auditory function of the heterozygous carriers of this Lebanese family, Mustapha et al. (1999) proposed that half of the normal amount of alpha-tectorin is sufficient to preserve the mechanical and electrical properties of the tectorial membrane. As a corollary, this led them to conclude that the mutations causing autosomal dominant DFNA8 and DFNA12 (601543) must have a dominant-negative effect. This, in turn, indicated that the mutated alpha-tectorin in DFNA8/12-affected individuals interacts with other molecules, i.e., normal alpha-tectorin, beta-tectorin (TECTB; 602653), or other components of the tectorial membrane. These results suggested that alpha-tectorin is involved in homeo- or heteromeric structures.
In a Swedish kindred with autosomal dominant nonsyndromic hearing impairment (601543), Balciuniene et al. (1999) identified a heterozygous 3170T-A transversion in exon 10 of the TECTA gene, resulting in a cys1057-to-ser (C1057S) substitution in one of the repeats of the zonadhesin/von Willebrand domain of the protein, which was predicted to cause a change in the crosslinking of the polypeptide that involves disulfide bonds. The mutation was found in all 9 severely affected members of the family and in some mildly affected members. The severe phenotype had severe hearing loss particularly at high frequencies (6 to 8 kHz) with a mean age at onset of 9 years. The milder phenotype had mild hearing loss only at high frequencies (4 to 6 kHz) with a mean age at onset of 19 years.
In a 3-generation French family in which 12 members had childhood-onset of mild to moderate progressive sensorineural hearing loss, Alloisio et al. (1999) found linkage of the disorder to the DFNA12 region (601543). Mutation screening of the TECTA gene identified a heterozygous 4857G-C missense mutation segregating with hearing loss in the 12 affected members. The cys1619-to-ser (C1619S) amino acid change was within the zonadhesin-like domain and may be involved in some aspect of tectorial membrane matrix assembly.
In affected members of a consanguineous Iranian family with hearing loss (603629), Naz et al. (2003) identified homozygosity for a 1-bp insertion, 649insC, in exon 5 of the TECTA gene, resulting in a frameshift. Affected subjects exhibited a severe hearing loss that was more pronounced in the 1,000-2,000 Hz frequency range, resulting in a flat to shallow U-shaped audiogram. The heterozygous carriers of the frameshift mutation had normal hearing thresholds. Naz et al. (2003) concluded that the distinctive audiometric profile provided a useful clinical marker to facilitate genetic diagnosis.
In affected members of a consanguineous Pakistani family with hearing loss (603629), Naz et al. (2003) identified homozygosity for a 1-bp deletion, 6037delG, in exon 20 of the TECTA gene, resulting in a frameshift. Testing demonstrated a flat to shallow U-shaped audiogram. The hearing loss was prelingual, bilateral, and moderate to severe. By history, the hearing impairment was nonprogressive. The heterozygous carriers of the frameshift mutation had normal hearing thresholds.
In affected members of a Spanish family with autosomal dominant nonsyndromic deafness (601543), Moreno-Pelayo et al. (2001) identified a heterozygous 5509T-G transversion in exon 17 of the TECTA gene, resulting in a cys1837-to-gly (C1837G) substitution in the zona pellucida domain. The substitution was predicted to disrupt interactions between the different tectorin polypeptides. The phenotype was characterized as postlingual, mid frequency, and progressive.
In 4 affected members of a Japanese family with autosomal dominant nonsyndromic hearing loss (601543), Iwasaki et al. (2002) identified a heterozygous 6063G-A transition in exon 20 of the TECTA gene, resulting in an arg2021-to-his (R2021H) substitution in the zona pellucida domain. The mean age at onset was 5 years; however, patients had a history of delayed speech development, suggesting a prelingual onset. Hearing loss was mid frequency and nonprogressive.
In affected members of a large Dutch family with autosomal dominant nonsyndromic hearing loss (601543), Plantinga et al. (2006) identified a heterozygous 5668C-T transition in the TECTA gene, resulting in an arg1890-to-cys (R1890C) substitution the zona pellucida domain. The hearing impairment was prelingual, nonprogressive, and affected mid frequencies with maximal hearing loss at 1 to 2 kHz.
In 10 affected members of a family with autosomal dominant nonsyndromic hearing loss (601543), Meyer et al. (2007) identified a heterozygous 5509T-C transition in the TECTA gene, resulting in a cys1837-to-arg (C1837R) substitution in the zona pellucida domain. The patients had childhood-onset mid frequency hearing loss with a U-shaped audiogram.
In 11 affected members of a Dutch family with autosomal dominant mid-frequency or flat hearing loss (601543), Collin et al. (2008) identified a heterozygous 5331G-A transition in exon 16 of the TECTA gene. The resultant amino acid change was a synonymous leu1777-to-leu (L1777L) substitution predicted to result in the loss of an exonic splice enhancer. RT-PCR analysis detected an aberrant TECTA transcript lacking exon 16, which deletes 37 residues from the protein just N-terminal to the zona pellucida domain. This same mutation was subsequently found in 2 of 36 additional patients with a similar phenotype. The mutation was not found in 250 control alleles.
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Balciuniene, J., Dahl, N., Borg, E., Samuelsson, E., Koisti, M. J., Pettersson, U., Jazin, E. E. Evidence for digenic inheritance of nonsyndromic hereditary hearing loss in a Swedish family. Am. J. Hum. Genet. 63: 786-793, 1998. [PubMed: 9718342] [Full Text: https://doi.org/10.1086/302012]
Balciuniene, J., Dahl, N., Jalonen, P., Verhoeven, K., Van Camp, G., Borg, E., Pettersson, U., Jazin, E. E. Alpha-tectorin involvement in hearing disabilities: one gene--two phenotypes. Hum. Genet. 105: 211-216, 1999. [PubMed: 10987647] [Full Text: https://doi.org/10.1007/s004390051091]
Collin, R. W. J., de Heer, A.-M. R., Oostrik, J., Pauw, R.-J., Plantinga, R. F., Huygen, P. L., Admiraal, R., de Brouwer, A. P. M., Strom, T. M., Cremers, C. W. R. J., Kremer, H. Mid-frequency DFNA8/12 hearing loss caused by a synonymous TECTA mutation that affects an exonic splice enhancer. Europ. J. Hum. Genet. 16: 1430-1436, 2008. [PubMed: 18575463] [Full Text: https://doi.org/10.1038/ejhg.2008.110]
Hughes, D. C., Legan, P. K., Steel, K. P., Richardson, G. P. Mapping of the alpha-tectorin gene (TECTA) to mouse chromosome 9 and human chromosome 11: a candidate for human autosomal dominant nonsyndromic deafness. Genomics 48: 46-51, 1998. [PubMed: 9503015] [Full Text: https://doi.org/10.1006/geno.1997.5159]
Iwasaki, S., Harada, D., Usami, S., Nagura, M., Takeshita, T., Hoshino, T. Association of clinical features with mutation of TECTA in a family with autosomal dominant hearing loss. Arch. Otolaryng. Head Neck Surg. 128: 913-917, 2002. [PubMed: 12162770] [Full Text: https://doi.org/10.1001/archotol.128.8.913]
Lee, M. L., Sciorra, L. J. Partial monosomy of the long arm of chromosome 11 in a severely affected child. Ann. Genet. 24: 51-53, 1981. [PubMed: 6971620]
Legan, P. K., Lukashkina, V. A., Goodyear, R. J., Kossl, M., Russell, I. J., Richardson, G. P. A targeted deletion in alpha-tectorin reveals that the tectorial membrane is required for the gain and timing of cochlear feedback. Neuron 28: 273-285, 2000. [PubMed: 11087000] [Full Text: https://doi.org/10.1016/s0896-6273(00)00102-1]
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Meyer, N. C., Alasti, F., Nishimura, C. J., Imanirad, P., Kahrizi, K., Riazalhosseini, Y., Malekpour, M., Kochakian, N., Jamali, P., Van Camp, G., Smith, R. J. H., Najmabadi, H. Identification of three novel TECTA mutations in Iranian families with autosomal recessive nonsyndromic hearing impairment at the DFNB21 locus. Am. J. Med. Genet. 143A: 1623-1629, 2007. [PubMed: 17431902] [Full Text: https://doi.org/10.1002/ajmg.a.31718]
Meyer, N. C., Nishimura, C. J., McMordie, S., Smith, R. J. H. Audioprofiling identifies TECTA and GJB2-related deafness segregating in a single extended pedigree. Clin. Genet. 72: 130-137, 2007. [PubMed: 17661817] [Full Text: https://doi.org/10.1111/j.1399-0004.2007.00828.x]
Moreno-Pelayo, M. A., del Castillo, I., Villamar, M., Romero, L., Hernandez-Calvin, F. J., Herraiz, C., Barbera, R., Navas, C., Moreno, F. A cysteine substitution in the zona pellucida domain of alpha-tectorin results in autosomal dominant, postlingual, progressive, mid frequency hearing loss in a Spanish family. (Letter) J. Med. Genet. 38: e13, 2001. Note: Electronic Article. [PubMed: 11333869] [Full Text: https://doi.org/10.1136/jmg.38.5.e13]
Mustapha, M., Weil, D., Chardenoux, S., Elias, S., El-Zir, E., Beckmann, J. S., Loiselet, J., Petit, C. An alpha-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual non-syndromic deafness, DFNB21. Hum. Molec. Genet. 8: 409-412, 1999. [PubMed: 9949200] [Full Text: https://doi.org/10.1093/hmg/8.3.409]
Naz, S., Alasti, F., Mowjoodi, A., Riazuddin, S., Sanati, M. H., Friedman, T. B., Griffith, A. J., Wilcox, E. R., Riazuddin, S. Distinctive audiometric profile associated with DFNB21 alleles of TECTA. J. Med. Genet. 40: 360-363, 2003. [PubMed: 12746400] [Full Text: https://doi.org/10.1136/jmg.40.5.360]
Plantinga, R. F., de Brouwer, A. P. M., Huygen, P. L. M., Kunst, H. P. M., Kremer, H., Cremers, C. W. R. J. A novel TECTA mutation in a Dutch DFNA8/12 family confirms genotype-phenotype correlation. J. Assoc. Res. Otolaryng. 7: 173-181, 2006. [PubMed: 16718611] [Full Text: https://doi.org/10.1007/s10162-006-0033-z]
Verhoeven, K., Van Laer, L., Kirschhofer, K., Legan, P. K., Hughes, D. C., Schatteman, I., Verstreken, M., Van Hauwe, P., Coucke, P., Chen, A., Smith, R. J. H., Somers, T., Offeciers, F. E., Van de Heyning, P., Richardson, G. P., Wachtler, F., Kimberling, W. J., Willems, P. J., Govaerts, P. J., Van Camp, G. Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic hearing impairment. Nature Genet. 19: 60-62, 1998. Note: Erratum: Nature Genet. 21: 449 only, 1999. [PubMed: 9590290] [Full Text: https://doi.org/10.1038/ng0598-60]