{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T02:57:51Z","timestamp":1784861871885,"version":"3.55.0"},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,26]],"date-time":"2022-02-26T00:00:00Z","timestamp":1645833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sequence alternations in mitochondrial genomes, especially in genes encoding mitochondrial tRNA (mt\u2010tRNA), were the important contributors to nonsyndromic hearing loss (NSHL); however, the molecular mechanisms remained largely undetermined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A maternally transmitted Chinese pedigree with NSHL underwent clinical, genetic, and biochemical assessment. PCR and direct sequence analyses were performed to detect mitochondrial DNA (mtDNA), <jats:italic>GJB2<\/jats:italic>, and <jats:italic>SLC26A4<\/jats:italic>\u00a0gene mutations from matrilineal relatives of this family. Mitochondrial functions including mitochondrial membrane potential (MMP), ATP, and ROS were evaluated in polymononuclear leukocytes (PMNs) derived from three deaf patients and three controls from this pedigree.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four of nine matrilineal relatives developed hearing loss at the variable age of onset. Two putative pathogenic mutations, m.5601C&gt;T in tRNA<jats:sup>Ala<\/jats:sup> and m.12311T&gt;C in tRNA<jats:sup>Leu(CUN)<\/jats:sup>, were identified via PCR\u2010Sanger sequencing, as well as 34 variants that belonged to mtDNA haplogroup G2b2. Intriguingly, m.5601C&gt;T mutation resided at very conserved nucleotide in the T\u03c8C loop of tRNA<jats:sup>Ala<\/jats:sup> (position 59), while the T\u2010to\u2010C substitution at position 12311\u00a0located at position 48 in the variable stem of tRNA<jats:sup>Leu(CUN)<\/jats:sup> and was believed to alter the aminoacylation and the steady\u2010state level of tRNA. Biochemical analysis revealed the impairment of mitochondrial functions including the significant reductions of ATP and MMP, whereas markedly increased ROS levels were found in PMNs derived from NSHL patients with m.5601C&gt;T and m.12311T&gt;C mutations. However, we did not detect any mutations in <jats:italic>GJB2<\/jats:italic> and <jats:italic>SLC26A4<\/jats:italic>\u00a0genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data indicated that mt\u2010tRNA<jats:sup>Ala<\/jats:sup> m.5601C&gt;T and tRNA<jats:sup>Leu(CUN)<\/jats:sup> 12311T&gt;C mutations were associated with NSHL.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24298","type":"journal-article","created":{"date-parts":[[2022,2,26]],"date-time":"2022-02-26T10:38:29Z","timestamp":1645871909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Maternally transmitted nonsyndromic hearing impairment may be associated with mitochondrial tRNA<sup>Ala<\/sup> 5601C&gt;T and tRNA<sup>Leu(CUN)<\/sup> 12311T&gt;C mutations"],"prefix":"10.1002","volume":"36","author":[{"given":"Xuejiao","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Quzhou 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