Frequency and origin of the c.2090T&gt;G p.(Leu697Trp) MYO3A variant associated with autosomal dominant hearing loss

Bueno, André Silva; Nunes, Kelly; Dias, Alex Marcel Moreira; Alves, Leandro Ucela; Mendes, Beatriz de Castro Andrade; Sampaio-Silva, Juliana; Smits, Jeroen J.; Meyer, Diogo; Lezirovitz, Karina; Mingroni‐Netto, Regina Célia

doi:10.1038/s41431-021-00891-0

Cited by 7 publications

(3 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1C). As a result, Bueno et al (2021) demonstrated that five families from Brazil, two out of them from this cohort, and one from The Netherlands, had their HL attributed to this variant and shared a common ancestor (Fig. 1C, Supplementary Table S3).…”

Section: Novel Brazilian Deafness Variants: Frequency In Our Cohortmentioning

confidence: 84%

See 1 more Smart Citation

Molecular and genetic characterization of a large Brazilian cohort presenting hearing loss

et al. 2021

Self Cite

View full text Add to dashboard Cite

Hearing loss is one of the most common sensory defects, affecting 5.5% of the worldwide population and significantly impacting health and social life. It is mainly attributed to genetic causes, but their relative contribution reflects the geographical region's socio-economic development. Extreme genetic heterogeneity with hundreds of deafness genes involved poses challenges for molecular diagnosis. Here we report the investigation of 542 hearing-impaired subjects from all Brazilian regions to search for genetic causes. Biallelic GJB2/GJB6 causative variants were identified in 12.9% (the lowest frequency was found in the Northern region, 7.7%), 0.4% carried GJB2 dominant variants, and 0.6% had the m.1555A > G variant (one aminoglycoside-related). In addition, other genetic screenings, employed in selected probands according to clinical presentation and presumptive inheritance patterns, identified causative variants in 2.4%. Ear malformations and auditory neuropathy were diagnosed in 10.8% and 3.5% of probands, respectively. In 3.8% of prelingual/perilingual cases, Waardenburg syndrome was clinically diagnosed, and in 71.4%, these diagnoses were confirmed with pathogenic variants revealed; seven out of them were novel, including one CNV. All these genetic screening strategies revealed causative variants in 16.2% of the cases. Based on causative variants in the molecular diagnosis and genealogy analyses, a probable genetic etiology was found in ~ 50% of the cases. The present study highlights the relevance of GJB2/GJB6 as a cause of hearing loss in all Brazilian regions and the importance of screening unselected samples for estimating frequencies. Moreover, when a comprehensive screening is not available, molecular diagnosis can be enhanced by selecting probands for specific screenings.

show abstract

Section: Novel Brazilian Deafness Variants: Frequency In Our Cohortmentioning

confidence: 84%

“…The protocols are described in Sampaio- Silva et al (2017), de Lima et al (2018), and Bueno et al (2021. In addition, the genes compositions of the NGS HL panels, both of 18 and 116 genes, are listed in Supplementary File S6.…”

Section: Exome/panel Ngsmentioning

confidence: 99%

Molecular and genetic characterization of a large Brazilian cohort presenting hearing loss

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the paper from Bueno et al [5], the authors demonstrate that in 3% of patients presenting with late onset autosomal dominant NSHL, the disease is linked to a specific variant in the MYO3A gene. This percentage is particularly high if one considers that it is quite difficult to identify the etiology of late-onset HL.…”

mentioning

confidence: 99%