Alpha-tectorin involvement in hearing disabilities: one gene - two phenotypes

Balciuniene, Jorune; Dahl, Niklas; Jalonen, Paula; Verhoeven, Kristien; Camp, Guy Van; Borg, Erik; Pettersson, Ulf; Jazin, Elena

doi:10.1007/s004390051091

Cited by 58 publications

(65 citation statements)

References 21 publications

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“…An additive effect of mutant alleles at the DFNA12 and DFNA2 loci was proposed to explain the variation in severity of a progressive nonsyndromic hearing loss observed in a Swedish family, wherein each separate locus was associated with a mild and sometimes undiagnosed phenotype, but both loci together were associated with a more severe phenotype (Balciuniene et al, 1998). Subsequently, mutations of the alpha tectorin gene TECTA were shown to underlie DFNA12 in this family, but no mutations were found in the gap junction gene GJB3 or the potassium channel gene KCNQ4, which were shown to be responsible for deafness at the DFNA2 locus in other families (Balciuniene et al, 1999). These results do not rule out digenic inheritance, because the DFNA2 locus may include an additional, as yet unidentified, gene that modulates the hearing loss associated with TECTA mutations.…”

Section: Digenic Inheritance and Hearing Loss In Mice And Humansmentioning

confidence: 78%

Strain background effects and genetic modifiers of hearing in mice

2006

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Genetic modifiers can be detected in mice by looking for strain background differences in inheritance or phenotype of a mutation. They can be mapped by analyses of appropriate linkage crosses and congenic lines, and modifier genes of large effect can be identified by positionalcandidate gene testing. Inbred strains of mice vary widely in onset and severity of age-related hearing loss (AHL), an important consideration when assessing hearing in mutant mice. At least 8 mapped loci and a mitochondrial variant (mt-Tr) are known to contribute to AHL in mouse strains; one locus (ahl) has been identified as a variant of the cadherin 23 gene (Cdh23 753A/G ). This variant also was shown to modify hearing loss associated with the Atp2b2 dfw-2J and Mass1 frings mutations. The hearing modifier (Moth1) of tubby (Tub tub ) mutant mice was shown to be a strain variant of the Mtap1a gene. Human hearing modifiers include DFNM1, which suppresses recessive deafness DFNB26, and a nuclear gene that modulates the severity of hearing loss associated with a mitochondrial mutation. Recently, a variant of the human ATP2B2 gene was shown to exacerbate hearing loss in individuals homozygous for a CDH23 mutation, similar to the Atp2b2 dfw-2J -Cdh23 753A/G interaction affecting hearing in mice. Because modifier genes and digenic inheritance are not always distinguishable, we also include in this review several examples of digenic inheritance of hearing loss that have been reported in both mice and humans. KeywordsModifier gene; Genetic background; Inbred mouse strain; Age-related hearing loss; Digenic inheritance; AHL; QTL Phenotypic diversity, strain background, and modifier genesGenetic modifiers are heritable factors capable of modifying the phenotype of a mutant gene without having an obvious effect on the normal condition. Modifier genes are found in all genetically mixed populations and their collective influence on a mutant phenotype is referred to as the genetic background effect or, in the case of inbred strains of mice, the strain background effect. Previously published review papers are replete with examples of the effects of modifier genes on the phenotypic diversity of a wide variety of genetic disorders in humans and mice (Barthold, 2004;Erickson, 1996;Houlston and Tomlinson, 1998;Montagutelli, 2000;Nadeau, 2001Nadeau, , 2003Romeo and McKusick, 1994;Slavotinek and Biesecker, 2003). Examples of modifier genes are especially prevalent in genetically heterogeneous phenotypes like sensorineural deafness (Slavotinek and Biesecker, 2003), and *Corresponding author. Fax: +1 207 288 6149. krj@jax.org (K.R. Johnson). NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript some reviews have focused specifically on modifiers of hearing (Ahituv and Avraham, 2002;Friedman et al., 2000;Haider et al., 2002;Riazuddin et al., 2002). Here, we present an updated review on strain background effects and genetic modifiers of hearing in mice including some related results from studies of human populations.G...

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Section: Digenic Inheritance and Hearing Loss In Mice And Humansmentioning

confidence: 78%

Strain background effects and genetic modifiers of hearing in mice

2006

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“…Differences in phenotype among DFNA8/12 families appear to be related to the position of the mutations in either the ZP or the ZA domain of a-tectorin as well as the nature of the amino acid substitution (Table 1). Mutations in the ZP and ZA domains have been related to mid-and high-frequency hearing impairment, respectively Verhoeven et al 1998;Govaerts et al 1998;Iwasaki et al 2002;Alloisio et al 1999;Balciuniene et al 1999;Pfister et al 2004;Moreno Pelayo et al 2001). Substitutions replacing cysteines have been implicated in progressive hearing impairment (Alloisio et al 1999;Balciuniene et al 1999;Pfister et al 2004;Moreno Pelayo et al 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Mutations affecting the ZP domain are associated with midfrequency hearing impairment, whereas mutations in the ZA domain are associated with hearing impairment primarily affecting the high frequencies (Table 1) Verhoeven et al 1998;Govaerts et al 1998;Iwasaki et al 2002;Alloisio et al 1999;Balciuniene et al 1999;Pfister et al 2004;Moreno Pelayo et al 2001). Hearing impairment can range from mild to severe and has prelingual or postlingual onset.…”

Section: Genotype-phenotype Correlationmentioning

confidence: 99%

A Novel TECTA Mutation in a Dutch DFNA8/12 Family Confirms Genotype–Phenotype Correlation

Plantinga

Brouwer

Huygen

et al. 2006

JARO

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A novel TECTA mutation, p.R1890C, was found in a Dutch family with nonsyndromic autosomal dominant sensorineural hearing impairment. In early life, presumably congenital, hearing impairment occurred in the midfrequency range, amounting to about 40 dB at 1 kHz. Speech recognition was good with all phoneme recognition scores exceeding 90%. An intact horizontal vestibuloocular reflex was found in four tested patients. The missense mutation is located in the zona pellucida (ZP) domain of a-tectorin. Mutations affecting the ZP domain of a-tectorin are significantly associated with midfrequency hearing impairment. Substitutions affecting other amino acid residues than cysteines show a significant association with hearing impairment without progression. Indeed, in the present family progression seemed to be absent. In addition, the presently identified mutation affecting the ZP domain resulted in a substantially lesser degree of hearing impairment than was previously reported for DFNA8/12 traits with mutations affecting the ZP domain of a-tectorin.

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“…Mutations in the TECTA gene have Genetic causes of NSHL in Iran N Mahdieh et al been found in both autosomal dominant and autosomal recessive HL (DFNA8/12 and DFNB21). [71][72][73][74] All presented missense mutations lead to the dominant form, whereas inactivating mutations bring about recessive HL. 75 TECTA mutations have been detected in Austrian, Belgian, French and Swedish families.…”

Section: Tecta Genementioning

confidence: 99%

Genetic causes of nonsyndromic hearing loss in Iran in comparison with other populations

et al. 2010

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Hearing loss (HL) is the most prevalent sensory defect affecting 1 in 500 neonates. Genetic factors are involved in half of the cases. The extreme heterogeneity of HL makes it difficult to analyze and determine the accurate genetic causes of the impairment. Up to now, 10 genes, namely, GJB2, GJB6, SLC26A4, TECTA, PJVK, Col11A2, Myo15A, TMC1, RDX and microRNA (miR-183), have been studied in an Iranian population. The prevalence of HL in Iran was estimated to be 2-3 times higher than that in other parts of the world. Here, the most common bases of congenital nonsyndromic hearing loss (NSHL) are discussed. We reviewed GJB2, GJB6 (large deletion), TECTA, SLC26A4 and PEJVK mutations, and studied their frequencies and distributions in different ethnic groups in 1934, 500, 121, 80 and 34 unrelated families throughout Iran, respectively. GJB2 mutation was the most common factor causing NSHL, with a mean frequency of 18.17% in the Iranian population. The importance of Iran's geographical location in the migration pathway from west to east through the silk route was also highlighted. SLC26A4 and TECTA mutations were the second and third main reasons of HL and accounted for up to 10 and 4% of prelingual HL in Iran, respectively. Mutations in GJB2, SLC26, TECTA and PJVK genes have an important role in HL in Iran and a screening test should be generated for better intervention and diagnosis programs.

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Alpha-tectorin involvement in hearing disabilities: one gene - two phenotypes

Cited by 58 publications

References 21 publications

Strain background effects and genetic modifiers of hearing in mice

Strain background effects and genetic modifiers of hearing in mice

A Novel TECTA Mutation in a Dutch DFNA8/12 Family Confirms Genotype–Phenotype Correlation

Genetic causes of nonsyndromic hearing loss in Iran in comparison with other populations

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