The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes

Laloi-Michelin, M.; Méas, T.; Ambonville, C.; Bellanné‐Chantelot, Christine; Beaufils, Sandrine; Massin, Pascale; Vialettes, B.; Gin, H.; Timsit, José; Bauduceau, B.; Bernard, Louis; Bertin, Éric; Blickle, Jean‐Frédéric; Cahen-Varsaux, J.; Cailleba, A; Casanova, S; Cathébras, P.; Charpentier, G.; Chedin, Pierre; Créa, T.; Delemer, Brigitte; Dubois‐Laforgue, Danièle; Duchemin, F.; Ducluzeau, Pierre-Henri; Bouhanick, Béatrice; Dusselier, L.; Gabreau, T.; Grimaldi, A.; Guerci, Bruno; Jacquin, Vincent; Kaloustian, E; Larger, Étienne; Lecleire–Collet, A.; Lorenzini, F.; Louis, J J; Mausset, J.; Murat, A.; Nadler-Fluteau, S.; Olivier, Frédérique; Paquis‐Flucklinger, Véronique; Paris-Bockel, D.; Raynaud, I.; Reznik, Yves; Riveline, JP; Schneebeli, Stéphane; Sonnet, E.; Sola-Gazagnes, A.; Thomas, Julie; Trabulsi, B.; Virally, Marie; Pj, Guillausseau

doi:10.1210/jc.2008-2680

Cited by 82 publications

(59 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are also a number of well-characterized multisystem syndromes due to inherited mtDNA point mutations that are associated with deafness. These include MIDD (Laloi-Michelin et al, 2009), MELAS (Deschauer et al, 2001) and MERRF (Chinnery et al, 2000; Fischel-Ghodsian, 2003), which are each associated with multiple clinical phenotypes. However, similar to most phenotypes observed in mtDNA genetic disorders, deafness is not an obligatory clinical feature.…”

Section: Human Mitochondrial Diseases Associated With Hearing Lossmentioning

confidence: 99%

Mitochondrial oxidative damage and apoptosis in age-related hearing loss

Someya

Prolla

2010

Mechanisms of Ageing and Development

139

108

View full text Add to dashboard Cite

Age-related hearing loss (AHL) is a universal feature of mammalian aging and is the most common sensory disorder in the elderly population. Experimental evidence suggests that mitochondrial dysfunction associated with reactive oxygen species (ROS) plays a central role in the aging process of cochlear cells. Although it is well established that mitochondria are the major source of ROS in the cell, specific molecular mechanisms of aging induced by ROS remain poorly characterized. Here we review the evidence that supports a central role for Bak-mediated mitochondrial apoptosis in AHL. We also propose that this mechanism may be of general relevance to age-related cell death in long-lived post-mitotic cells of multiple tissues, providing an opportunity for a targeted therapeutic intervention in human aging.

show abstract

Section: Human Mitochondrial Diseases Associated With Hearing Lossmentioning

confidence: 99%

Mitochondrial oxidative damage and apoptosis in age-related hearing loss

Someya

Prolla

2010

Mechanisms of Ageing and Development

139

108

View full text Add to dashboard Cite

show abstract

“…As demonstrated in other studies (Bai and Wong, 2004;Genasetti et al, 2007;Sakiyama et al, 2011), using ARMS, we were able to detect variable proportions of the m.1624C>T mutation. The proportion of heteroplasmic mtDNA is generally one determinant of phenotypic severity (Choi et al, 2010;Laloi-Michelin et al, 2009). Compared with the severely affected Leigh syndrome-like siblings with homoplasmic m.1624C>T mutation, our heteroplasmic cases showed milder phenotypes with respect to the age of onset and clinical features (Table 5); the lower proportion of mutant mtDNA might be responsible for this.…”

Section: Discussionmentioning

confidence: 75%

Heteroplasmic m.1624C>T mutation of the mitochondrial tRNAVal gene in a proband and his mother with repeated consciousness disturbances

et al. 2012

View full text Add to dashboard Cite

“…Interestingly, similar symptoms have been associated with some patients with another mitochondrial disorder, maternally inherited diabetes and deafness, which highlights the clinical overlap which often exists with mitochondrial diseases [37,38] . Neuropathy, ataxia and retinitis pigmentosa syndrome is usually due to the ATP6 T8993G mutation.…”

Section: Mtdna Mutationsmentioning

confidence: 80%

The Importance of Mitochondria in Age-Related and Inherited Eye Disorders

2010

View full text Add to dashboard Cite

Mitochondria are critical for ocular function as they represent the major source of a cell’s supply of energy and play an important role in cell differentiation and survival. Mitochondrial dysfunction can occur as a result of inherited mitochondrial mutations (e.g. Leber’s hereditary optic neuropathy and chronic progressive external ophthalmoplegia) or stochastic oxidative damage which leads to cumulative mitochondrial damage and is an important factor in age-related disorders (e.g. age-related macular degeneration, cataract and diabetic retinopathy). Mitochondrial DNA (mtDNA) instability is an important factor in mitochondrial impairment culminating in age-related changes and pathology, and in all regions of the eye mtDNA damage is increased as a consequence of aging and age-related disease. It is now apparent that the mitochondrial genome is a weak link in the defenses of ocular cells since it is susceptible to oxidative damage and it lacks some of the systems that protect the nuclear genome, such as nucleotide excision repair. Accumulation of mitochondrial mutations leads to cellular dysfunction and increased susceptibility to adverse events which contribute to the pathogenesis of numerous sporadic and chronic disorders in the eye.

show abstract

The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes

Abstract: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD.

Cited by 82 publications

References 27 publications

Mitochondrial oxidative damage and apoptosis in age-related hearing loss

Mitochondrial oxidative damage and apoptosis in age-related hearing loss

Heteroplasmic m.1624C>T mutation of the mitochondrial tRNAVal gene in a proband and his mother with repeated consciousness disturbances

The Importance of Mitochondria in Age-Related and Inherited Eye Disorders

Contact Info

Product

Resources

About