J Korean Med Sci.  2023 Dec;38(48):e355. 10.3346/jkms.2023.38.e355.

Prevalence and Clinical Characteristics of Mitochondrial DNA Mutations in Korean Patients With Sensorineural Hearing Loss

• Joo SY
• Jang SH
• Kim JA
• Kim SJ
• Kim B
• Kim HY
• Choi JY
• Gee HY
• Jung J

• KMID: 2549162
• DOI: http://doi.org/10.3346/jkms.2023.38.e355

Abstract

Background
Mutations in mitochondrial DNA (mtDNA) are associated with several genetic disorders, including sensorineural hearing loss. However, the prevalence of mtDNA mutations in a large cohort of Korean patients with hearing loss has not yet been investigated. Thus, this study aimed to investigate the frequency of mtDNA mutations in a cohort of with pre- or post-lingual hearing loss of varying severity.
Methods
A total of 711 Korean families involving 1,099 individuals were evaluated. Six mitochondrial variants associated with deafness (MTRNR1 m.1555A>G, MTTL1 m.3243A>G, MTCO1 m.7444G>A and m.7445A>G, and MTTS1 m.7471dupC and m.7511T>C) were screened using restriction fragment length polymorphism. The prevalence of the six variants was also analyzed in a large control dataset using whole-genome sequencing data from 4,534 Korean individuals with unknown hearing phenotype.
Results
Overall, 12 of the 711 (1.7%) patients with hearing loss had mtDNA variants, with 10 patients from independent families positive for the MTRNR1 m.1555A>G mutation and 2 patients positive for the MTCO1 m.7444G>A mutation. The clinical characteristics of patients with the mtDNA variants were characterized by post-lingual progressive hearing loss due to the m.1555A>G variant (9 of 472; 1.9%). In addition, 18/4,534 (0.4%) of the Korean population have mitochondrial variants associated with hearing loss, predominantly the m.1555A>G variant.
Conclusion
A significant proportion of Korean patients with hearing loss is affected by the mtDNA variants, with the m.1555A>G variant being the most prevalent. These results clarify the genetic basis of hearing loss in the Korean population and emphasize the need for genetic testing for mtDNA variants.

Keyword

Mitochondrial DNA; Restriction Fragment Length Polymorphism; Sensorineural Hearing Loss

Figure

• 

  Fig. 1 Detection rate of pathogenic mtDNA variants in the YUHL cohort and pedigree information summarizing segregation analysis. (A) Detection rate of mtDNA mutations that cause deafness in the YUHL cohort. Among the 711 families screened for mtDNA mutations, 10 unrelated hearing loss patients with the m.1555A>G variant and 2 patients with the m.7444G>A variant are identified. (B) Detection rate of deafness-causing mtDNA mutations in a group of YUHL patients with moderate-to-profound post-lingual hearing loss. (C) Pedigree and segregation results of families carrying m.1555A>G variant. (D) Pedigree and segregation results of families with m.7444G>A variant. Individuals highlighted in red were those available for RFLP and Sanger sequencing. ‘+’ indicated individuals with the mtDNA variants.mtDNA = mitochondrial DNA, YUHL = Yonsei University Hearing Loss.

• 

  Fig. 2 Audiograms of m.1555A>G variant carriers. The transparent blue line depicts the individual thresholds, the average of the right and left ear (except for YUHL847-21 and 1054-21). The thresholds of the affected ear are indicated for YUHL847-21 and 1054-21. The black line represents the average of ten audiograms.YUHL = Yonsei University Hearing Loss.

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