Aberrant transcript produced by a splice donor site deletion in the TECTA gene is associated with autosomal dominant deafness in a Brazilian family

Lezirovitz, Karina; Batissoco, Ana Carla; Lima, Fernanda Teresa de; Auricchio, Maria T.B.M.; Nonose, Renata Watanabe; Santos, Simone R. dos; Guilherme, Luiza; Oiticica, Jeanne; Mingroni-Netto, Regina Célia

doi:10.1016/j.gene.2012.09.023

Cited by 14 publications

(10 citation statements)

References 20 publications

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“…33 It was recently reported to generate aberrant splicing products by exon 16 skipping, but not by reading frame disruption, in lymphoblastoid cell lines from affected subjects in a Brazilian family. 34 Mutations in the TECTA gene result in either AD (DFNA8/12) or AR (DFNB21) SNHL. 35,36 This variant affects the zonadhesion-zona (ZA-ZP) interdomain, and a previous study described nonprogressive, slightly down-sloping or flat-type, moderate to severe hearing loss, which is compatible with the audiogram configuration observed in patient SB106-198.…”

Section: Genetics In Medicine | Volume 17 | Number 11 | November 2015mentioning

confidence: 99%

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Kim

Park

et al. 2015

Genetics in Medicine

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Purpose: This study was designed to delineate genetic contributions, if any, to sporadic forms of mild to moderate sensorineural hearing loss (SNHL) not related to GJB2 mutations (DFNB1) in a pediatric population. Methods:We recruited 11 non-DFNB1 simplex cases of mild to moderate SNHL in children. We applied whole-exome sequencing to all 11 probands. We used a filtering strategy assuming that de novo variants of known autosomal dominant (AD) deafness genes, biallelic mutations in autosomal recessive (AR) genes, monoallelic mutations in X chromosome genes for males, and digenic inheritance could be associated. Candidate variants first were prioritized with allele frequency in public databases and confirmed by a phase or a segregation test in each family. Additional information from the literature or public databases was used to identify strong candidate variants.Results: Strong candidate variants were detected in 5 of 11 probands (45.4%). A diverse mode of inheritance implicated the sporadic occurrence of the phenotype. AR mutations in OTOGL and SERPINB6 and digenic inheritance involving two deafness genes, GPR98 and PDZ7, were detected. A de novo AD mutation also was detected in TECTA and MYH14. No syndromic feature was detected in individuals with GPR98/PDZ7 or MYH14 variants in our cohort at this moment. Conclusion:Mild to moderate pediatric SNHL, even if sporadic, features a strong genetic etiology and can manifest via diverse modes of inheritance. In addition, a multidisciplinary approach should be used for a correct diagnosis. Genet Med advance online publication 26 February 2015

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Section: Genetics In Medicine | Volume 17 | Number 11 | November 2015mentioning

confidence: 99%

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Kim

Park

et al. 2015

Genetics in Medicine

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“…In addition, we detected the heterozygous small deletion c.5383þ5_5383þ8delGTGA in TECTA (OMIM: 602574), [25][26][27] a gene causative of autosomal dominant and recessive deafness. After these results, new family assessment of HL demonstrated that the father, and the paternal aunt and grandfather also presented with deafness ( Fig.…”

Section: Family Frp-426mentioning

confidence: 99%

Expanding the Genetic Landscape of Usher-Like Phenotypes

Fuster-García

García‐García

Jaijo

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Usher syndrome (USH) is a rare disorder characterized by retinitis pigmentosa (RP) and sensorineural hearing loss. Several genes are responsible for the disease, but not all cases are explained by mutations in any of these, supporting the fact that there remain other unknown genes that have a role in the syndrome. We aimed to find the genetic cause of presumed USH patients lacking pathogenic mutations in the known USH genes. METHODS. Whole exome sequencing was performed on a priori USH-diagnosed subjects from nine unrelated families, which had shown negative results for an USH-targeted panel in a previous study. RESULTS. We identified possible pathogenic variants in six of the studied families. One patient harbored mutations in REEP6 and TECTA, each gene tentatively causative of one of the two main symptoms of the disease, mimicking the syndrome. In three patients, only the retinal degeneration causative mutations were detected (involving EYS, WDR19, and CNGB1 genes). Another family manifested a dementia-linked retinal dystrophy dependent on an allele dosage in the GRN gene. Last, another case presented a homozygous mutation in ASIC5, a gene not yet associated with USH. CONCLUSIONS. Our findings demonstrate that pending cases should be clinically and genetically carefully assessed, since more patients than expected may be either related phenocopies or affected by a more complex disease encompassing additional symptoms rather than classical USH.

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“…TECTA is a highly polymorphic gene [10], and functional analyses of the variants of TECTA are not achieved easily, except in limited cases [21], [22]. Therefore, confirming that the detected variant of TECTA truly accounts for hearing loss and excluding other genes that may be responsible for the phenotype are extremely difficult without proper linkage data.…”

Section: Introductionmentioning

confidence: 99%

Whole-Exome Sequencing Identifies a Novel Genotype-Phenotype Correlation in the Entactin Domain of the Known Deafness Gene TECTA

et al. 2014

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Postlingual progressive hearing loss, affecting primarily the high frequencies, is the clinical finding in most cases of autosomal dominant nonsyndromic hearing loss (ADNSHL). The molecular genetic etiology of ADNSHL is extremely heterogeneous. We applied whole-exome sequencing to reveal the genetic etiology of high-frequency hearing loss in a mid-sized Korean family without any prior linkage data. Whole-exome sequencing of four family members (two affected and two unaffected), together with our filtering strategy based on comprehensive bioinformatics analyses, identified 21 potential pathogenic candidates. Sanger validation of an additional five family members excluded 20 variants, leaving only one novel variant, TECTA c.710C>T (p.T237I), as the strongest candidate. This variant resides in the entactin (ENT) domain and co-segregated perfectly with non-progressive high-frequency hearing loss in the family. It was absent among 700 ethnically matched control chromosomes, and the T237 residue is conserved among species, which supports its pathogenicity. Interestingly, this finding contrasted with a previously proposed genotype-phenotype correlation in which variants of the ENT domain of TECTA were associated with mid-frequency hearing loss. Based upon what we observed, we propose a novel “genotype to phenotype” correlation in the ENT domain of TECTA. Our results shed light on another important application of whole-exome sequencing: the establishment of a novel genotype-phenotype in the molecular genetic diagnosis of autosomal dominant hearing loss.

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Aberrant transcript produced by a splice donor site deletion in the TECTA gene is associated with autosomal dominant deafness in a Brazilian family

Cited by 14 publications

References 20 publications

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Expanding the Genetic Landscape of Usher-Like Phenotypes

Whole-Exome Sequencing Identifies a Novel Genotype-Phenotype Correlation in the Entactin Domain of the Known Deafness Gene TECTA

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