The mitochondrial transfer RNAAsp A7551G mutation may contribute to the clinical expression of deafness associated with the A1555G mutation in a pedigree with hearing impairment

Zhang, Jing; Lü, Bo; Xia, Wei‑Wei; Fang, Bin; Ding, Xiaoxia; Hu, Guangwei

doi:10.3892/mmr.2018.9790

Cited by 7 publications

(11 citation statements)

References 29 publications

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“…Compared with previous studies, if the AmAn was included, the penetrances of mitochondrial A1555G-induced hearing loss ranged from 13.0% to 71.4%, with an average of 45.75%. While the AmAn was excluded, the penetrances of A1555G-induced deafness ranged from 8.0% to 51.5%, with an average of 23.85% (Table 6) [34][35][36][37][38][39]. Whereas in other seven families with C1494T mutation, the penetrances of hearing loss ranged from 6.3% to 42.8% (with AmAn, average: 18.8%).…”

Section: Discussionmentioning

confidence: 99%

Screening for deafness-associated mitochondrial 12S rRNA mutations by using a multiplex allele-specific PCR method

et al. 2020

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Mitochondrial 12S rRNA A1555G and C1494T mutations are the major contributors to hearing loss. As patients with these mutations are sensitive to aminoglycosides, mutational screening for 12S rRNA is therefore recommended before the use of aminoglycosides. Most recently, we developed a novel multiplex allele-specific PCR (MAS-PCR) that can be used for detecting A1555G and C1494T mutations. In the present study, we employed this MAS-PCR to screen the 12S rRNA mutations in 500 deaf patients and 300 controls from 5 community hospitals. After PCR and electrophoresis, two patients with A1555G and one patient with C1494T were identified, this was consistent with Sanger sequence results. We further traced the origin of three Chinese pedigrees. Clinical evaluation revealed variable phenotypes of hearing loss including severity, age at onset and audiometric configuration in these patients. Sequence analysis of the mitochondrial genomes from matrilineal relatives suggested the presence of three evolutionarily conserved mutations: tRNACys T5802C, tRNALys A8343G and tRNAThr G15930A, which may result the failure in tRNAs metabolism and lead to mitochondrial dysfunction that was responsible for deafness. However, the lack of any functional variants in GJB2, GJB3, GJB6 and TRMU suggested that nuclear genes may not play active roles in deafness expression. Hence, aminoglycosides and mitochondrial genetic background may contribute to the clinical expression of A1555G/C1494T-induced deafness. Our data indicated that the MAS-PCR was a fast, convenience method for screening the 12S rRNA mutations, which was useful for early detection and prevention of mitochondrial deafness.

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Section: Discussionmentioning

confidence: 99%

Screening for deafness-associated mitochondrial 12S rRNA mutations by using a multiplex allele-specific PCR method

et al. 2020

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“…To see the contributions of GJB2 variants to clinical expression of MIDD, we conducted a mutational screening by using PCR amplification of the exons of GJB2 gene in matrilineal individuals (DM-101: II-3, II-6 and III-5; DM-102: II-5, II-8, II-10 and III-7), the primer sequence for amplification of GJB2 gene were: forward-5ʹ-TATGACACTCCCCAGCACAG-3ʹ, and reverse-5ʹ-GGGCAATGCTTAAACTGGC-3ʹ. 30 After PCR amplification and direct Sanger sequence analysis, the data were compared with the wild-type versions of GJB2 sequence (GenBank Accessible Number: M86849) to identify mutations/variants. 30 …”

Section: Methodsmentioning

confidence: 99%

“… 30 After PCR amplification and direct Sanger sequence analysis, the data were compared with the wild-type versions of GJB2 sequence (GenBank Accessible Number: M86849) to identify mutations/variants. 30 …”

Section: Methodsmentioning

confidence: 99%

Mutational Analysis of Mitochondrial tRNA Genes in 200 Patients with Type 2 Diabetes Mellitus

Lin¹,

Zhang²,

Jin³

et al. 2021

IJGM

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Objective: Previous studies showed that variants in mitochondrial DNA (mtDNA) are associated with type 2 diabetes mellitus (T2DM). However, the relationships between mitochondrial tRNA (mt-tRNA) variants and T2DM remain poorly understood. Methods: In this study, we performed a mutational screening of 22 mt-tRNA genes in a cohort of 200 Han Chinese subjects with T2DM and 200 control subjects through PCR-Sanger sequencing. The identified mt-tRNA variants were assessed for their pathogenicity via the phylogenetic approach, structural and functional analysis. Furthermore, two Han Chinese pedigrees with maternally inherited diabetes and deafness (MIDD) were reported by clinical and genetic assessments. Results: A total of 49 genetic variants in mt-tRNA genes were identified; among them, 31 variants (17 pathogenic/likely pathogenic) were absent in controls, located at extremely conserved nucleotides, may have potential structural and functional significance, thereby considered to be T2DM-associated variants. In addition, sequence analysis of entire mitochondrial genomes of the matrilineal relatives from two MIDD pedigrees revealed the occurrence of tRNA Leu(UUR) A3243G and T3290C mutations, as well as sets of polymorphisms belonging to mitochondrial haplogroups F2 and D4. However, the lack of any functional variants in connexin 26 gene (GJB2) and tRNA 5-methylaminomethyl-2-thiouridylate (TRMU) suggested that nuclear genes may not play active roles in clinical expression of MIDD in these pedigrees. Conclusion: Our data indicated that mt-tRNA variants were associated with T2DM, screening for mt-tRNA pathogenic mutations was recommended for early detection and prevention of mitochondrial diabetes.

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“…The following Pcr thermocycling conditions were used: initial denaturation at 95˚C for 5 min; 30 cycles of 94˚C for 10 sec, 60˚C for 30 sec and 72˚C for 1 min; and a final extension at 72˚C for 5 min. Subsequently, the 24 PCR products were purified and analyzed using Sanger sequence technology as previously described (20). The complete mtdna genes of the matrilineal relatives from the two families (ii-10, ii-8 and ii-5 in Family 1; I-2, II-6 and II-8 in Family 2) were also amplified by Pcr and sequenced as above.…”

Section: Methodsmentioning

confidence: 99%

“…1). The primers used were as described previously (17,19,20). The primers for PCR amplification of GJB2 were: Forward, 5'-TaT Gac acT ccc caG cac aG-3' and reverse, 5'-GGG GCA ATG CTT AAA CTG GC-3'.…”

Section: Methodsmentioning

confidence: 99%

Low penetrance of hearing loss in two Chinese families carrying the mitochondrial tRNASer(UCN) mutations

et al. 2020

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Mutations in mitochondrial dna (mtdna), especially in mitochondrial 12S rrna and transfer rna(trna) Ser(ucn) genes, are impor tant causes of non-syndromic hearing loss. However, the molecular mechanism underlying mt-trna mutations in clinical hearing impairment are not fully understood. The present study assessed the molecular characterization of two chinese families with non-syndromic hearing loss, who both exhibited very low penetrance of deafness (9.1 and 12.5% for Family 1 and 2, respectively). Mutational analysis of the complete mtdna genes identified the presence of cytochrome c oxidase 1/trna Ser(ucn) G7444a and trna Ser(ucn) c7492T mutations, together with polymorphisms belonging to human mitochondrial haplogroup d4 and G2b, respectively. Moreover, the G7444a and c7492T mutations occurred at highly conserved trna Ser(ucn) nucleotides and may cause trna metabolism failure, which is involved in mitochondrial translation defects. Therefore, the G7444a and c7492T mutations may lead to the mitochondrial dysfunction that responsible for deafness. However, the absence of any functional variants in Gap junction β-2, Solute carrier Family 26 Member 4 and Trna 5-methylaminomethyl-2-thiouridylate methyltransferase suggested that nuclear genes may not play active roles in the occurrence of deafness. in the present study, the observed incomplete penetrance of hearing loss and mild mitochondrial dysfunction indicated that mtdna G7444A and C7492T mutations are insufficient to produce the deafness phenotype. Therefore, other risk factors such as environmental factors and epigenetic regulation may be involved in the pathogenesis of hearing loss in the families recruited in the present study.

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The mitochondrial transfer RNAAsp A7551G mutation may contribute to the clinical expression of deafness associated with the A1555G mutation in a pedigree with hearing impairment

Cited by 7 publications

References 29 publications

Screening for deafness-associated mitochondrial 12S rRNA mutations by using a multiplex allele-specific PCR method

Screening for deafness-associated mitochondrial 12S rRNA mutations by using a multiplex allele-specific PCR method

Mutational Analysis of Mitochondrial tRNA Genes in 200 Patients with Type 2 Diabetes Mellitus

Low penetrance of hearing loss in two Chinese families carrying the mitochondrial tRNASer(UCN) mutations

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