R75Q dominant mutation in <i>GJB2</i> gene silenced by the in cis recessive mutation c.35delG

Iossa, Sandra; Chinetti, Viviana; Corvino, Virginia; Marciano, Elio; Franzè, Annamaria

doi:10.1002/ajmg.a.33630

Cited by 6 publications

(4 citation statements)

References 11 publications

(13 reference statements)

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“…Future experiments will have to show whether arginine 75 is able to be substituted and whether cis V37I somehow induces conformational change of the protein to rescue the R75Q phenotype. In addition to a previous study, 12 our study emphasizes the importance of cis mutations with R75Q as the gene effect of R75Q can be modulated depending on the type of the additional mutation.…”

Section: Discussionsupporting

confidence: 56%

“…However, the family study revealed that the affected sibling of the patient did not have this allele and indicated that R75Q was silenced by c.35delG as c.35delG causes early termination of translation. 12 …”

Section: Discussionmentioning

confidence: 99%

“…Another interesting case showed that R75Q, a dominant GJB2 mutation, was silenced by the cis recessive mutation c.35delG. 12 Herein, we present a Korean patient with non-syndromic hearing loss caused by the cis R75Q mutation with V37I, which arose de novo in the father and was inherited by the patient.…”

Section: Introductionmentioning

confidence: 92%

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Non-syndromic hearing loss caused by the dominant cis mutation R75Q with the recessive mutation V37I of the GJB2 (Connexin 26) gene

Kim

Jung²,

Lee

et al. 2015

Exp Mol Med

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GJB2 alleles containing two cis mutations have been rarely found in non-syndromic hearing loss. Herein, we present a Korean patient with non-syndromic hearing loss caused by the R75Q cis mutation with V37I, which arose de novo in the father and was inherited by the patient. Biochemical coupling and hemichannel permeability assays were performed after molecular cloning and transfection of HEK293T cells. Student's t-tests or analysis of variance followed by Tukey's multiple comparison test was used as statistical analysis. Biochemical coupling was significantly reduced in connexin 26 (Cx26)-R75Q- and Cx26-V37I-transfected cells, with greater extent in Cx26-R75Q and Cx26-R75Q+V37I cells. Interestingly, our patient and his father with the mutations had more residual hearing compared with patients with the dominant mutation alone. Although the difference in hemichannel activity between R75Q alone and R75Q in combination with V37I failed to reach significance, it is of note that there is a possibility that V37I located upstream of R75Q might have the ability to ameliorate R75Q expression. Our study emphasizes the importance of cis mutations with R75Q, as the gene effect of R75Q can be modulated depending on the type of additional mutation.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

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Non-syndromic hearing loss caused by the dominant cis mutation R75Q with the recessive mutation V37I of the GJB2 (Connexin 26) gene

Kim

Jung²,

Lee

et al. 2015

Exp Mol Med

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“…Though relatively rare, the GJB2 c.35delG homozygous mutation, which is the most prevalent mutation in Caucasians, could also contribute to late postnatal onset hearing loss (Pagarkar et al, 2006). There are also some GJB2 pathogenic mutations associated with post-lingual hearing impairment, such as p. T55N, p.R75Q, p.D179N, and p.C202F (Morle et al, 2000;Primignani et al, 2003;Melchionda et al, 2005;Iossa et al, 2010), which are inherited as autosomal dominant patterns .…”

Section: Phenotype-genotype Correlation Analysismentioning

confidence: 99%

Phenotypic Heterogeneity of Post-lingual and/or Milder Hearing Loss for the Patients With the GJB2 c.235delC Homozygous Mutation

Wang

Gao

Guan

et al. 2021

Front. Cell Dev. Biol.

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ObjectiveTo report the phenotypic heterogeneity of GJB2 c.235delC homozygotes associated with post-lingual and/or milder hearing loss, and explore the possible mechanism of these unconditional phenotypes.MethodsMutation screening of GJB2 was performed on all ascertained members from Family 1006983 and three sporadic patients by polymerase chain reaction (PCR) amplification and Sanger sequencing. Next generation sequencing (NGS) was successively performed on some of the affected members and normal controls from Family 1006983 to explore additional possible genetic codes. Reverse transcriptase–quantitative PCR was conducted to test the expression of Connexin30.ResultsWe identified a Chinese autosomal recessive hearing loss family with the GJB2 c.235delC homozygous mutation, affected members from which had post-lingual moderate to profound hearing impairment, and three sporadic patients with post-lingual moderate hearing impairment, instead of congenital profound hearing loss. NGS showed no other particular variants. Overexpression of Connexin30 in some of these cases was verified.ConclusionPost-lingual and/or moderate hearing impairment phenotypes of GJB2 c.235delC homozygotes are not the most common phenotype, revealing the heterogeneity of GJB2 pathogenic mutations. To determine the possible mechanism that rescues part of the hearing or postpones onset age of these cases, more cases are required to confirm both Connexin30 overexpression and the existence of modifier genes.

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R75Q de novo dominant mutation of GJB2 in a Chinese family with hearing loss and palmoplantar keratoderma

Jiang

Huang

et al. 2014

International Journal of Pediatric Otorhinolaryngology

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R75Q dominant mutation in GJB2 gene silenced by the in cis recessive mutation c.35delG

Cited by 6 publications

References 11 publications

Non-syndromic hearing loss caused by the dominant cis mutation R75Q with the recessive mutation V37I of the GJB2 (Connexin 26) gene

Non-syndromic hearing loss caused by the dominant cis mutation R75Q with the recessive mutation V37I of the GJB2 (Connexin 26) gene

Phenotypic Heterogeneity of Post-lingual and/or Milder Hearing Loss for the Patients With the GJB2 c.235delC Homozygous Mutation

R75Q de novo dominant mutation of GJB2 in a Chinese family with hearing loss and palmoplantar keratoderma

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