Audiological Evidence of Frequent Hereditary Mild, Moderate and Moderate-to-Severe Hearing Loss

Маркова, Т Г; Alekseeva, N. N.; Lalayants, M. R.; Рыжкова, О. П.; Shatokhina, Olga; Галеева, Н. М.; Bliznetz, E. A.; Belov, Oleg; Чибисова, С. С.; Polyakov, A. V.; Таварткиладзе, Г. А.

doi:10.3390/jpm12111843

Cited by 4 publications

(3 citation statements)

References 48 publications

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“…As mild hearing-loss is being increasingly diagnosed at an earlier age [28], this presents prognostic and management uncertainty for both families [29] and clinicians [30]. This study provides evidence for a genetic basis for many mild hearing loss cases adding to the emerging body of literature describing genotypes in mild and moderate hearing loss cohorts [31,32].…”

Section: Discussionmentioning

confidence: 75%

The congenital hearing phenotype in GJB2 in Queensland, Australia: V37I and mild hearing loss predominates

Liddle,

Kriukelis,

Gabbett

et al. 2024

Preprint

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Guidelines recommend GJB2 (connexin 26) and GJB6 (connexin 30) testing for bilateral non-syndromic sensorineural hearing loss (SNHL). However, associated audiological phenotypes vary. There is limited Australian data on GJB2 variant frequency and associated phenotypes. Audiograms from a paediatric cohort with SNHL, predominantly identified through newborn hearing screening and carrying GJB2 variants and/or a GJB6 deletion (GJB6-D13S11830) were retrospectively reviewed (n = 127). Two thirds were homozygous or compound heterozygous for pathogenic or likely pathogenic variants of GJB2 and/or GJB6 (n = 80). The most frequent variant, c.109G > A, occurred in homozygous (n = 32), compound heterozygous (n = 8) and heterozygous (n = 5) states. Compared to homozygous/compound heterozygous carriage of other GJB2 variants, c.109G > A positive individuals (homozygous/compound heterozygous) were more likely to have mild HL at their initial (p = 0.00004) and latest audiograms (p = 0.0004). Homozygous/compound heterozygous carriage of c.35delG was associated with moderately-severe or greater HL at both initial (p = 0.007) and latest (p = 0.007) audiograms. The c.101T > C variant presented with milder HL and U-shaped audiograms (p = 0.02). In this agnostically identified cohort, mild HL predominated in GJB2/GJB6 carriers in contrast to previous studies targeting individuals with significant loss. Consequently, c.109G > A, associated with milder phenotypes, was the most frequent. This data provides valuable, balanced prognostic information for preconception, prenatal and paediatric counselling of couples and families carrying these variants.

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Section: Discussionmentioning

confidence: 75%

The congenital hearing phenotype in GJB2 in Queensland, Australia: V37I and mild hearing loss predominates

Liddle,

Kriukelis,

Gabbett

et al. 2024

Preprint

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show abstract

“…Some genes are associated with very specific levels and ages of onset hearing loss; for example, MYO15A is associated with autosomal recessive congenital profound bilateral sensorineural hearing loss (OMIM #600316) (Chang et al, 2018; Rehman et al, 2016). STRC has been identified as the most common genetic cause of mild to moderate sensorineural hearing loss (Han et al, 2021; Markova et al, 2022; Simi et al, 2021). MPZL2 was first identified as a gene causing mild to moderate hearing loss in two independent studies published in 2018.…”

Section: Discussionmentioning

confidence: 99%

Recurrent missense variant identified in two unrelated families with MPZL2‐related hearing loss, expanding the variant spectrum associated with DFNB111

Lo,

Blair,

Yamamoto

et al. 2024

American J of Med Genetics Pt A

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MPZL2‐related hearing loss is a rare form of autosomal recessive hearing loss characterized by progressive, mild sloping to severe sensorineural hearing loss. Thirty‐five previously reported patients had biallelic truncating variants in MPZL2, with the exception of one patient with a missense variant of uncertain significance and a truncating variant. Here, we describe the clinical characteristics and genotypes of five patients from four families with confirmed MPZL2‐related hearing loss. A rare missense likely pathogenic variant [NM_005797.4(MPZL2):c.280C>T,p.(Arg94Trp)] located in exon 3 was confirmed to be in trans with a recurrent pathogenic truncating variant that segregated with hearing loss in three of the patients from two unrelated families. This is the first recurrent likely pathogenic missense variant identified in MPZL2. Apparently milder or later‐onset hearing loss associated with rare missense variants in MPZL2 indicates that some missense variants in this gene may cause a milder phenotype than that resulting from homozygous or compound heterozygous truncating variants. This study, along with the identification of truncating loss of function and missense MPZL2 variants in several diverse populations, suggests that MPZL2‐related hearing loss may be more common than previously appreciated and demonstrates the need for MPZL2 inclusion in hearing loss testing panels.

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“…As a congenital anomaly that has genetic origins, most of the cases are postlingual SNHL [ 9 ]. Wingard and Zhao suggested that postlingual SNHL may result from impaired active cochlear amplification due to Cx26 deficiency [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Unusual phenotype in 35delG mutation: a case report

Yeral,

Seneldir,

Karakoc

et al. 2024

J Med Case Reports

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Background Mutations in the GJB2 gene, which encodes the protein connexin 26 and is involved in inner ear homeostasis, are identified in approximately 50% of patients with autosomal recessive nonsyndromic hearing loss, making it one of the primary causes of prelingual nonsyndromic hearing loss in various populations. The 35delG mutation, one of the most common mutations of the GJB2 gene, usually causes prelingual, bilateral mild to profound, nonprogressive sensorineural hearing loss. Case presentation We present an unusual case of an 18-year-old Turkish female with heterozygous 35delG mutation and postlingual, profound-sloping, progressive and fluctuating unilateral sensorineural hearing loss. The phenotype is different from the usual findings. Conclusions The 35delG mutation causing hearing loss may not always be reflected in the phenotype as expected and therefore may have different audiologic manifestations.

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Audiological Evidence of Frequent Hereditary Mild, Moderate and Moderate-to-Severe Hearing Loss

Cited by 4 publications

References 48 publications

The congenital hearing phenotype in GJB2 in Queensland, Australia: V37I and mild hearing loss predominates

The congenital hearing phenotype in GJB2 in Queensland, Australia: V37I and mild hearing loss predominates

Recurrent missense variant identified in two unrelated families with MPZL2‐related hearing loss, expanding the variant spectrum associated with DFNB111

Unusual phenotype in 35delG mutation: a case report

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