Novel genotype–phenotype correlation of functionally characterized
            <i>LMX1A</i>
            variants linked to sensorineural hearing loss

Lee, Sang Yeon; Han, Jin Hee; Carandang, Marge; Kim, Min Young; Kim, Bong Gi; Yi, Nayoung; Kim, Jin-Ho; Kim, Bong Jik; Oh, Doo Yi; Koo, Ja Won; Lee, Jun Ho; Oh, Seung Ha; Choi, Byung Yoon

doi:10.1002/humu.24095

Cited by 14 publications

(18 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In most cases, the pedigrees indicated an autosomal dominant inheritance pattern. In one family, a de novo heterozygous missense variant (c.595A>G:p.Arg199Gly) was previously reported [ 18 ]. Four of the six variants were in the homeodomain, and the remaining two were truncated variants in LIM2 and the C-terminus, respectively ( Figure 1 c).…”

Section: Resultsmentioning

confidence: 99%

“…LMX1A , a LIM homeobox TF, has been recently implicated in non-syndromic deafness. LMX1A plays a vital role in ear patterning, regulating the morphogenesis of inner ear structures [ 18 ]. To date, only nine LMX1A variants have been reported in the literature.…”

Section: Discussionmentioning

confidence: 99%

“…Schrauwen et al [ 43 ] described a Pakistani family with an LMX1A recessive C-terminus missense variant (c.1106T>C;p.Ile369Thr) associated with profound SNHL. In recent studies, we reported five LMX1A heterozygous variants (c.595A>G:p.Arg199Gly, c.622C>T;p.Arg208*, c.719A>G;p.Gln240Arg, c.721G>A;p.Val241Met, and c.887dup;p.Gln297Thrfs*41) in five Korean families and one LMX1A heterozygous variant (c.686C>A; p.Ala229Asp) in a Polish family [ 18 , 44 ]. Together, these results suggest that alterations in LMX1A are associated with dominantly inherited asymmetric deafness.…”

Section: Discussionmentioning

confidence: 99%

“…Together, these results suggest that alterations in LMX1A are associated with dominantly inherited asymmetric deafness. In these variants, audiological severity correlated with the extent of transcriptional activation, measured in a luciferase-reporter assay, implying a genotype–phenotype correlation [ 18 ]. Our study expands the genotypic spectrum of LMX1A in DFNA7 by identifying a novel variant (c.331del:p.Gln111Argfs*7), in addition to demonstrating audiologic asymmetry (SH421).…”

Section: Discussionmentioning

confidence: 99%

“…The resulting reads were compared with the UCSC hg19 reference genome, and non-synonymous single-nucleotide polymorphisms (SNPs) were filtered at a depth of 40; dbSNP138 was filtered out, except for the flagged SNP. Disease-causing variants were detected in this study using a comprehensive filtering process and bioinformatics analyses, as described previously [ 16 , 17 , 18 ]. The pathogenic potential of the novel variants identified herein was evaluated according to the ACMG/AMP guidelines developed for hearing loss [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

Genetic Load of Alternations of Transcription Factor Genes in Non-Syndromic Deafness and the Associated Clinical Phenotypes: Experience from Two Tertiary Referral Centers

Han

Lee

et al. 2022

Biomedicines

Self Cite

View full text Add to dashboard Cite

Sensorineural hearing loss is one of the most common inherited sensory disorders. Functional classifications of deafness genes have shed light on genotype- and mechanism-based pharmacological approaches and on gene therapy strategies. In this study, we characterized the clinical phenotypes and genotypes of non-syndromic deafness caused by transcription factor (TF) gene variants, one of the functional classifications of genetic hearing loss. Of 1280 probands whose genomic DNA was subjected to molecular genetic testing, TF genes were responsible for hearing loss in 2.6%. Thirty-three pathogenic variants, including nine novel variants, accounting for non-syndromic deafness were clustered in only four TF genes (POU3F4, POU4F3, LMX1A, and EYA4), which is indicative of a narrow molecular etiologic spectrum of TF genes, and the functional redundancy of many other TF genes, in the context of non-syndromic deafness. The audiological and radiological characteristics associated with the four TF genes differed significantly, with a wide phenotypic spectrum. The results of this study reveal the genetic load of TF gene alterations among a cohort with non-syndromic hearing loss. Additionally, we have further refined the clinical profiles associated with TF gene variants as a basis for a personalized, genetically tailored approach to audiological rehabilitation.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Genetic Load of Alternations of Transcription Factor Genes in Non-Syndromic Deafness and the Associated Clinical Phenotypes: Experience from Two Tertiary Referral Centers

Han

Lee

et al. 2022

Biomedicines

Self Cite

View full text Add to dashboard Cite

show abstract

Correlation between the etiology of severe hearing loss and endolymphatic hydrops

Park,

Han,

Lee

et al. 2024

Eur Arch Otorhinolaryngol

View full text Add to dashboard Cite

Purpose This study aimed to investigate correlation between the presence of endolymphatic hydrops(EH) and factors such as causes of hearing loss, patient age, duration of deafness, and results of vestibular function tests. Methods We retrospectively reviewed medical charts of 128 ears of cochlear implantees who were not considered relevant to Meniere’s disease. Results When comparing group with genetic variants of GJB2, SLC26A4, LMX1A and other genetic mutation group, the proportion of vestibular EH and cochlear EH found in group with genetic variants of GJB2, SLC26A4, LMX1A was significantly higher than group with other genetic etiology (p < 0.01) or the group with all the other causes of hearing loss (p < 0.01). The rate of vestibular and cochlear EH detection was higher in younger patients (41.5% and 35.4%) than in older patients (25.4% and 20.6%). A higher ratio of vestibular and cochlear EH was observed in patients with a longer duration of deafness (37.5% and 31.3%) than those with a shorter duration of deafness (29.7% and 25.0%). The group with vestibular EH showed a higher incidence of abnormal findings in the caloric test (42.9%) than the group without vestibular EH (28.2%). Conclusion Patients with genetic variants of GJB2, SLC26A4, LMX1A, younger patients, those with longer deaf durations showed a higher prevalence of vestibular and cochlear EH, implying EH appears to be formed as a developmental disorder in association with a certain set of genetic variants, rather than a phenotypic marker as a result of severe to profound hearing loss.

show abstract

Update on CD164 and LMX1A genes to strengthen their causative role in autosomal dominant hearing loss

et al. 2022

View full text Add to dashboard Cite

Novel genotype–phenotype correlation of functionally characterized LMX1A variants linked to sensorineural hearing loss

Cited by 14 publications

References 23 publications

Genetic Load of Alternations of Transcription Factor Genes in Non-Syndromic Deafness and the Associated Clinical Phenotypes: Experience from Two Tertiary Referral Centers

Genetic Load of Alternations of Transcription Factor Genes in Non-Syndromic Deafness and the Associated Clinical Phenotypes: Experience from Two Tertiary Referral Centers

Correlation between the etiology of severe hearing loss and endolymphatic hydrops

Update on CD164 and LMX1A genes to strengthen their causative role in autosomal dominant hearing loss

Contact Info

Product

Resources

About