In order to determine the role of mitochondrial DNA mutations in thyroid tumorigenesis, Abu-Amero et al. (2005) sequenced the entire mtDNA from 24 thyroid tumor specimens and four thyroid cancer cell lines.  Somatic mutations were identified in 37% of primary thyroid carcinomas (PTC) and among 25% of multinodular hyperplasia cases.  Most mutations were nucleotide substitutions resulting in missense mutations.  Of these sequence changes, 14 were nonsynonymous and 36 were synonymous.  Eight synonymous sequence changes were detected in the ND1 gene. In a later study, Abu-Amero et al. (2006) sequenced the entire coding region of mitochondrial DNA for 26 MTC patients and 119 normal population controls.  Of the MTC patients, 13 were sporadic, nine had MEN 2A, one had MEN 2B, and three had FMTC.  In 20 MTC samples, 41 nonsynonymous mutations were detected; nine were from sporadic MTC and 11 were from familial MTC and MEN2.  Also, 15 synonymous mtDNA sequence variants were found in MTC samples, seven of them were novel.  Twenty seven mutations were transversions; 22 nonsynonymous and six synonymous.  These transversion variants were only detected in FMTC/MEN2 while transition variants were mainly found in sporadic MTC cases.  Two nonsynonymous variants (C>G and C>A) were found within the MT-ND1 gene, one of these mutations was predicted to be damaging.  None of these mutations were present in the normal controls, suggesting that mtDNA mutations may be involved in MTC tumorigenesis and progression.  Abu-Amero and Bosley (2006) studied further the molecular and biological characteristics of mitochondria in patients with Leber hereditary optic neuropathy (LHON)-like optic neuropathies.  Thirty five patients (21 males and 14 females) and 159 matched controls from Saudi Arabia were included in this study.  Forty one non-synonymous mtDNA sequence variants were identified in LHON patients; 14 were pathogenic.  Of these variants, 21 were in complex I, seven in complex III, five in complex IV, six in complex V, one in tRNA glutamine, and one in 12S rRNA.  Similar to previous reports on mutation association with LHON, these mtDNA changes were transitions.  The common G3460A mtDNA mutation of the MT-ND1 gene was found in patients 1-6.  Two additional non-pathogenic variants, C4040G and T4216C, were also found in this gene.

Mkaouar-Rebai et al. (2007) found a T3396C transition in the ND1 gene in one family with nonsyndromic hearing loss, which was absent in the other patients and in 100 controls.  In a review of mitochondrial mutations in Tunisian patients with mitochondrial disorders, Mkaouar-Rebai et al. (2013) reported a single case with hypertrophic cardiomyopathy and deafness who presented with the ND1 m.3395A>G mutation and the tRNA(Ile) m.4316A>G variation.