Prevalencia de las mutaciones 35delG en el gen GJB2, del (GJB6-D13S1830) en el gen GJB6, Q829X en el gen OTOF y A1555G en el gen del ARNr 12S mitocondrial en sujetos con hipoacusia neurosensorial no sindrómica de inicio congénito o en la infancia

Gallo-Terán, J.; Morales‐Angulo, Carmelo; Rodríguez-Ballesteros, Montserrat; Moreno-Pelayo, Miguel A.; Castillo, Ignacio del; Moreno, Felipe

doi:10.1016/s0001-6519(05)78649-0

Cited by 15 publications

(3 citation statements)

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“…In contrast, our 38% incidence of AD and 14% of X-linked SNHL are higher than expected [ 44 ]. This might reflect the consequences of pre-screening, which excluded the most common AR ( GJB2/GJB6 and OTOF ) and mitochondrial ( MT-RNR1 ) mutations [ 2 , 31 , 45 ]. However, since in our patients 50% (4/8) of causative dominant variants were de novo (2 in ACTG1 , 1 in GATA3 ; and 1 in COL4A5 , Table 2 ) it might also be the consequence of using an unbiased NGS panel, able to identify unexpected de novo variants.…”

Section: Discussionmentioning

confidence: 99%

“…This percentage strongly declines for AD hearing loss, especially with the increase in the age of onset [ 5 , 48 ]. In our series, as in most of published studies [ 5 , 48 , 51 ], prior to comprehensive genetic testing, patients were prescreened for common deafness mutations (in our cohort, GJB2/GJB6 , OTOF and MT-RNR1 , selected for their high prevalence in Spain [ 7 , 31 ]). Mutations in the GJB2 gene are among the most frequent causes for congenital hearing loss.…”

Section: Discussionmentioning

confidence: 99%

“…Between September 2014 and March 2017, 50 consecutive patients (21 male, 29 female) with syndromic/non-syndromic SNHL were selected after excluding non-genetic causes and causative variants in the DFNB1 (GJB2/GJB6) , OTOF and MT-RNR1 loci, considered the most frequent causes of hereditary deafness in Spain [ 7 , 31 ]. Consent was obtained from patients or their parents.…”

Section: Methodsmentioning

confidence: 99%

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Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients

et al. 2018

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BackgroundSensorineural hearing loss (SNHL) is the most common sensory impairment. Comprehensive next-generation sequencing (NGS) has become the standard for the etiological diagnosis of early-onset SNHL. However, accurate selection of target genomic regions (gene panel/exome/genome), analytical performance and variant interpretation remain relevant difficulties for its clinical implementation.MethodsWe developed a novel NGS panel with 199 genes associated with non-syndromic and/or syndromic SNHL. We evaluated the analytical sensitivity and specificity of the panel on 1624 known single nucleotide variants (SNVs) and indels on a mixture of genomic DNA from 10 previously characterized lymphoblastoid cell lines, and analyzed 50 Spanish patients with presumed hereditary SNHL not caused by GJB2/GJB6, OTOF nor MT-RNR1 mutations.ResultsThe analytical sensitivity of the test to detect SNVs and indels on the DNA mixture from the cell lines was > 99.5%, with a specificity > 99.9%. The diagnostic yield on the SNHL patients was 42% (21/50): 47.6% (10/21) with autosomal recessive inheritance pattern (BSND, CDH23, MYO15A, STRC [n = 2], USH2A [n = 3], RDX, SLC26A4); 38.1% (8/21) autosomal dominant (ACTG1 [n = 3; 2 de novo], CHD7, GATA3 [de novo], MITF, P2RX2, SOX10), and 14.3% (3/21) X-linked (COL4A5 [de novo], POU3F4, PRPS1). 46.9% of causative variants (15/32) were not in the databases. 28.6% of genetically diagnosed cases (6/21) had previously undetected syndromes (Barakat, Usher type 2A [n = 3] and Waardenburg [n = 2]). 19% of genetic diagnoses (4/21) were attributable to large deletions/duplications (STRC deletion [n = 2]; partial CDH23 duplication; RDX exon 2 deletion).ConclusionsIn the era of precision medicine, obtaining an etiologic diagnosis of SNHL is imperative. Here, we contribute to show that, with the right methodology, NGS can be transferred to the clinical practice, boosting the yield of SNHL genetic diagnosis to 50–60% (including GJB2/GJB6 alterations), improving diagnostic/prognostic accuracy, refining genetic and reproductive counseling and revealing clinically relevant undiagnosed syndromes.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0375-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients

et al. 2018

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Analyses of del(GJB6‐D13S1830) and del(GJB6‐D13S1834) deletions in a large cohort with hearing loss: Caveats to interpretation of molecular test results in multiplex families

Pandya

O’Brien

Kovasala

et al. 2020

Molec Gen & Gen Med

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Background Mutations involving the closely linked GJB2 and GJB6 at the DFNB1 locus are a common genetic cause of profound congenital hearing loss in many populations. In some deaf GJB2 heterozygotes, a 309 kb deletion involving the GJB6 has been found to be the cause for hearing loss when inherited in trans to a GJB2 mutation. Methods We screened 2,376 probands from a National DNA Repository of deaf individuals. Results Fifty‐two of 318 heterozygous probands with pathogenic GJB2 sequence variants had a GJB6 deletion. Additionally, eight probands had an isolated heterozygous GJB6 deletion that did not explain their hearing loss. In two deaf subjects, including one proband, a homozygous GJB6 deletion was the cause for their hearing loss, a rare occurrence not reported to date. Conclusion This study represents the largest US cohort of deaf individuals harboring GJB2 and GJB6 variants, including unique subsets of families with deaf parents. Testing additional members to clarify the phase of GJB2/GJB6 variants in multiplex families was crucial in interpreting clinical significance of the variants in the proband. It highlights the importance of determining the phase of GJB2/GJB6 variants when interpreting molecular test results especially in multiplex families with assortative mating.

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Molecular approach of auditory neuropathy

Silva

Piatto

Maníglia

2015

Brazilian Journal of Otorhinolaryngology

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Prevalencia de las mutaciones 35delG en el gen GJB2, del (GJB6-D13S1830) en el gen GJB6, Q829X en el gen OTOF y A1555G en el gen del ARNr 12S mitocondrial en sujetos con hipoacusia neurosensorial no sindrómica de inicio congénito o en la infancia

Cited by 15 publications

References 31 publications

Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients

Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients

Analyses of del(GJB6‐D13S1830) and del(GJB6‐D13S1834) deletions in a large cohort with hearing loss: Caveats to interpretation of molecular test results in multiplex families

Molecular approach of auditory neuropathy

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