Non-syndromic Hearing Impairment in a Hungarian Family with the m.7510T&gt;C Mutation of Mitochondrial tRNASer(UCN) and Review of Published Cases

Komlósi, Katalin; Maász, Anita; Kisfali, Péter; Hadzsiev, Kinga; Bene, Judit; Melegh, Béla; Ablonczy, Mária; Németh, Krisztína; Fekete, György

doi:10.1007/8904_2012_187

Cited by 4 publications

(9 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We describe a Finnish family with the m.7510T>C mutation and the associated variable phenotype in four affected family members. The m.7510T>C mutation has previously been reported in four families (Hutchin et al., ; del Castillo et al., ; Labay et al., ; Komlósi et al., ). In two families, the phenotype was an isolated HI (del Castillo et al., ; Labay et al., ) while in the other two families additional neurologic symptoms were described (Hutchin et al., ; Komlósi et al., ).…”

Section: Discussionmentioning

confidence: 84%

“…When considering the wide range in the age of onset related to this mutation, the clinical phenotype thus far associated with this mutation might still be incomplete. The level of heteroplasmy does not seem to explain the phenotypic variability as the mutation has been described in homoplasmic state in three of the four previously reported families (del Castillo et al., ; Labay et al., ; Komlósi et al., ). In our study, patient I‐2 was clearly heteroplasmic and her HI was mild.…”

Section: Discussionmentioning

confidence: 85%

“…The m.7510T>C mutation has previously been reported in four families (Hutchin et al, 2000;del Castillo et al, 2002;Labay et al, 2008;Komlósi et al, 2013). In two families, the phenotype was an isolated HI (del Castillo et al, 2002;Labay et al, 2008) while in the other two families additional neurologic symptoms were described (Hutchin et al, 2000;Komlósi et al, 2013). In the Hungarian family, the proband was reported to have coordination problems and delayed fine motor skills in his first clinical examination at the age of 4 years (Komlósi et al, 2013) Besides clumsiness, possibly indicative of ataxia, the neurologic examination was unremarkable.…”

Section: Discussionmentioning

confidence: 90%

“…In two families, the phenotype was an isolated HI (del Castillo et al., ; Labay et al., ) while in the other two families additional neurologic symptoms were described (Hutchin et al., ; Komlósi et al., ). In the Hungarian family, the proband was reported to have coordination problems and delayed fine motor skills in his first clinical examination at the age of 4 years (Komlósi et al., ) Besides clumsiness, possibly indicative of ataxia, the neurologic examination was unremarkable. Intellectual disability was reported in the maternal aunt of the proband in a UK family, but interpreted as being due to birth asphyxia (Hutchin et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…Based on the reported cases, both the age of onset and severity of HI related to the m.7510T>C mutation are variable. In the Hungarian family, the only person unaffected by HI was only 3 years old (Komlósi et al., ) In the Spanish family, three unaffected persons were 11–16 years of age, and the fourth unaffected family member was already 31 years old at the time of investigations (del Castillo et al., ). When considering the wide range in the age of onset related to this mutation, the clinical phenotype thus far associated with this mutation might still be incomplete.…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

The m.7510T>C mutation: Hearing impairment and a complex neurologic phenotype

et al. 2017

View full text Add to dashboard Cite

ObjectivesMutations in mitochondrial DNA cause a variety of clinical phenotypes ranging from a mild hearing impairment (HI) to severe encephalomyopathy. The MT‐TS1 gene is a hotspot for mutations causing HI. The m.7510T>C mutation in MT‐TS1 has been previously associated with non‐syndromic HI in four families from different ethnic backgrounds.Materials and MethodsWe describe the clinical, genetic, and histopathological findings in a Finnish family with the heteroplasmic m.7510T>C mutation in mitochondrial DNA.ResultsThe family proband presented with a progressive mitochondrial disease phenotype including migraine, epilepsy, mild ataxia, and cognitive impairment in addition to HI. One young adult presented with HI only. Other family members had a mild phenotype comprising ataxia and tremor in addition to HI. Mutation heteroplasmy was 90% in the blood of maternal grandmother and ≥99% in the muscle and blood of the three other family members. Muscle histology was consistent with mitochondrial myopathy in three family members. The mitochondrial haplogroup of the family was a different branch of the haplogroup H than in the previous reports of this mutation.ConclusionOur results suggest that, in addition to sensorineural HI, the m.7510T>C mutation is associated with a spectrum of mitochondrial disease clinical features including migraine, epilepsy, cognitive impairment, ataxia, and tremor, and with evidence of mitochondrial myopathy.

show abstract

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

The m.7510T>C mutation: Hearing impairment and a complex neurologic phenotype

et al. 2017

View full text Add to dashboard Cite

show abstract

Mitochondrial tRNASer(UCN) mutations associated non-syndromic sensorineural hearing loss in Chinese families

Zhang,

Wu,

Yuan

et al. 2024

Heliyon

View full text Add to dashboard Cite

Ancient mitochondrial DNA pathogenic variants putatively associated with mitochondrial disease

Serbezov

Karachanak-Yankova

Nesheva

2020

Preprint

View full text Add to dashboard Cite

23Mitochondrial DNA variants associated with diseases are widely studied in contemporary 24 populations, but their prevalence has not yet been investigated in ancient populations. The publicly 25 available AmtDB database contains 1443 ancient mtDNA Eurasian genomes from different 26 periods. The objective of this study was to use this data to establish the presence of pathogenic 27 mtDNA variants putatively associated with mitochondrial diseases in ancient populations. The 28 clinical significance, pathogenicity prediction and contemporary frequency of mtDNA variants 29 were determined using online platforms. The analyzed ancient mtDNAs contain six variants 30 designated as being "confirmed pathogenic" in modern patients. The oldest of these, m.7510T>C 31 in the MT-TS1 gene, was found in a sample from the Neolithic period dated 5800-5400 BCE. All 32 six have well established clinical association, and their pathogenic effect is corroborated by very 33 low population frequencies in contemporary populations. In addition, ten variants designated as 34 possibly or likely pathogenic were detected. The oldest of these were two variants in the MT-TD 35 gene, m.7543A>G and m.7554G>A, from Neolithic samples dated 8205-7700 BCE. A novel 36 mutation in contemporary populations, m.4440G>A in the MT-TM gene, is established in 12 ancient 37 mtDNA samples from different periods ranging from 2800 BCE to 920 CE. The pathogenic effect 38 of these possibly/likely pathogenic mutations is not yet well established, and further research is 39 warranted. All detected mutations putatively associated with mitochondrial disease in ancient 40 mtDNA samples are in tRNA coding genes. Most of these mutations are in a mt-tRNA type (Model 41 2) that is characterized by loss of D-loop/T-loop interaction. Seven mutations are located in CS-42 Anticodon stem, 4 are located in AS-Acceptor stem, 2 in TS-TΨC stem, and single mutations are 43 found in DL-Dihydrouridine Loop, CL-Anticodon Loop and DS-Dihydrouridine stem. Exposing 44 pathogenic variants in ancient human populations expands our understanding of their origin. 65 severity of the clinical and biochemical phenotype caused by pathogenic mtDNA mutations has 66however been found to be roughly proportionate to the percent mutant heteroplasmy (10, 11). 67Nucleotide polymorphisms accumulate in mtDNA during human evolution forming mitochondrial 68 haplogroups, and these also might alter the penetrance of mitochondrial diseases (12). Specific 69 subclades of haplogroup J, for example, have been shown to affect the penetrance and 70 pathogenicity of Leber's hereditary optic neuropathy (13). Certain mtDNA mutations and 71 haplogroups are also predictors of both lifespan and risk of various age-associated disease, 72 including degenerative diseases, cancer, diabetes, heart failure, sarcopenia and Parkinson's disease 73 (14). 74 We had previously performed whole-genome sequencing on 25 Thracian mtDNA samples dated 75 3000-2000 BCE, and 608 mtDNA variants were detected (15). Only one of these, however, 7...

show abstract

Non-syndromic Hearing Impairment in a Hungarian Family with the m.7510T>C Mutation of Mitochondrial tRNASer(UCN) and Review of Published Cases

Cited by 4 publications

References 19 publications

The m.7510T>C mutation: Hearing impairment and a complex neurologic phenotype

The m.7510T>C mutation: Hearing impairment and a complex neurologic phenotype

Mitochondrial tRNASer(UCN) mutations associated non-syndromic sensorineural hearing loss in Chinese families

Ancient mitochondrial DNA pathogenic variants putatively associated with mitochondrial disease

Contact Info

Product

Resources

About