Splicing mutations of GSDME cause late-onset non-syndromic hearing loss / 临床耳鼻咽喉头颈外科杂志
Journal of Clinical Otorhinolaryngology Head and Neck Surgery
; (12): 30-37, 2024.
Article
en Zh
| WPRIM
| ID: wpr-1011098
Biblioteca responsable:
WPRO
ABSTRACT
Objective:
To dentify the genetic and audiological characteristics of families affected by late-onset hearing loss due to GSDMEgene mutations, aiming to explore clinical characteristics and pathogenic mechanisms for providing genetic counseling and intervention guidance.Methods:
Six families with late-onset hearing loss from the Chinese Deafness Genome Project were included. Audiological tests, including pure-tone audiometry, acoustic immittance, speech recognition scores, auditory brainstem response, and distortion product otoacoustic emission, were applied to evaluate the hearing levels of patients. Combining with medical history and physical examination to analyze the phenotypic differences between the probands and their family members. Next-generation sequencing was used to identify pathogenic genes in probands, and validations were performed on their relatives by Sanger sequencing. Pathogenicity analysis was performed according to the American College of Medical Genetics and Genomics Guidelines. Meanwhile, the pathogenic mechanisms of GSDME-related hearing loss were explored combining with domestic and international research progress.Results:
Among the six families with late-onset hearing loss, a total of 30 individuals performed hearing loss. The onset of hearing loss in these families ranged from 10 to 50 years(mean age 27.88±9.74 years). In the study, four splicing mutations of the GSDME were identified, including two novel variants c. 991-7C>G and c. 1183+1G>T. Significantly, the c. 991-7C>G was a de novo variant. The others were previously reported variants c. 991-1G>C and c. 991-15_991-13del, the latter was identified in three families. Genotype-phenotype correlation analysis revealed that probands with the c. 991-7C>G and c. 1183+1G>T performed a predominantly high-frequency hearing loss. The three families carrying the same mutation exhibited varying degrees of hearing loss, with an annual rate of hearing deterioration exceeding 0.94 dB HL/year. Furthermore, follow-up of interventions showed that four of six probands received intervention(66.67%), but the results of intervention varied.Conclusion:
The study analyzed six families with late-onset non-syndromic hearing loss linked to GSDME mutations, identifying four splicing variants. Notably, c. 991-7C>G is the first reported de novo variant of GSDME globally. Audiological analysis revealed that the age of onset generally exceeded 10 years,with variable effectiveness of interventions.Palabras clave
Texto completo:
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Base de datos:
WPRIM
Asunto principal:
Linaje
/
Sordera
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Pérdida Auditiva
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Pérdida Auditiva Sensorineural
/
Mutación
Límite:
Adolescent
/
Adult
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Child
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Humans
Idioma:
Zh
Revista:
Journal of Clinical Otorhinolaryngology Head and Neck Surgery
Año:
2024
Tipo del documento:
Article