Risk of developing a mitochondrial DNA deletion disorder

Chinnery, Patrick F.; DiMauro, Salvatore; Shanske, Sara; Schon, Eric A.; Zeviani, Massimo; Mariotti, Caterina; Carrara, Fernanda Souza Angotti; Lombès, Anne; Laforêt, Pascal; Ogier, H.; Jaksch, Michaela; Lochmüller, Hanns; Horvath, Rita; Deschauer, Marcus; Thorburn, David R.; Bindoff, Laurence A.; Poulton, Joanna; Taylor, Robert W.; Matthews, J. N. S.; Turnbull, Douglass M.

doi:10.1016/s0140-6736(04)16851-7

Cited by 188 publications

(126 citation statements)

References 29 publications

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“…In this study, with whole-exome sequencing, we did not identify pathogenic mutations in any of the known mtDNA maintenance genes (El-Hattab and Scaglia 2013;Suomalainen and Isohanni 2010) to disclose the genetic aetiology of the disease in Patients 1 and 2, but further studies are ongoing to evaluate the role of the candidate genes identified by whole-exome sequencing (unpublished data provided by Dr. Javad Nadaf, Dr. Somayyeh Fahiminiya and Prof. Jacek Majewski, Department of Human Genetics, McGill University and Genome Quebec Innovation Center, Montreal, Canada) associated with these novel MDDS phenotypes. Most single mtDNA deletions are thought to be sporadic and thus not genetically transmitted (Chinnery et al 2004), but multiple mtDNA deletions can be inherited as an autosomal dominant or recessive trait (Zeviani et al 1990;Nishino et al 1999). Our two patients with a KSS/ Pearson-like phenotype presented with minor multiple deletions in addition to a major large-scale mtDNA deletion, which led us to suggest a genetic origin of the mtDNA arrangements leading to these clinical phenotypes.…”

Section: Discussionmentioning

confidence: 67%

Mitochondrial DNA Depletion and Deletions in Paediatric Patients with Neuromuscular Diseases: Novel Phenotypes

et al. 2015

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Objective: To study the clinical manifestations and occurrence of mtDNA depletion and deletions in paediatric patients with neuromuscular diseases and to identify novel clinical phenotypes associated with mtDNA depletion or deletions.Methods: Muscle DNA samples from patients presenting with undefined encephalomyopathies or myopathies were analysed for mtDNA content by quantitative real-time PCR and for deletions by long-range PCR. Direct sequencing of mtDNA maintenance genes and whole-exome sequencing were used to study the genetic aetiologies of the diseases. Clinical and laboratory findings were collected.

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Section: Discussionmentioning

confidence: 67%

Mitochondrial DNA Depletion and Deletions in Paediatric Patients with Neuromuscular Diseases: Novel Phenotypes

et al. 2015

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“…In the pedigrees that we reviewed, affected subjects were not restricted to older brothers or sisters, and the proportion of mutant mtDNA was not significantly higher in older siblings (Ballinger et al 1992;Bernes et al 1993;Hammans et al 1993;De Vries et al 1994;Puoti et al 2003). Moreover, epidemiological studies showed no correlation between maternal age and risk of inheritance of pathogenic deletion-mutant mtDNA (Brenner et al 1998;Chinnery et al 2004). Thus, although we cannot directly apply our findings to humans with pathogenic mutant mtDNAs, an understanding of the underlying ''Tail'' is the proportion of DmtDNA in the tail of the newborn mito-mice.…”

Section: Resultsmentioning

confidence: 96%

Deletion-Mutant mtDNA Increases in Somatic Tissues but Decreases in Female Germ Cells With Age

et al. 2007

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“…Algunas mutaciones ocurren de novo y la madre no es portadora; en ese caso se estima un riesgo de repetición alrededor de 1/24 (4%) (16). Si la madre es portadora de la mutación mitocondrial, habría un riesgo de transmisión variable.…”

Section: Riesgos Reproductivosunclassified

Valoración ética de las nuevas opciones reproductivas en las enfermedades mitocondriales

Moya

2016

Acta bioeth.

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Resumen: Las enfermedades mitocondriales son un grupo de desórdenes clínicamente heterogéneo con manifestaciones clínicas muy variables y alta tasa de morbi-mortalidad. Tienen complejas implicancias en la reproducción, ya que los riesgos de repetición en la familia son variables, 25% en las formas autosómicas recesivas, alrededor de 4% en los casos de mutaciones mitocondriales de novo, y un riesgo incierto pero elevado si la madre es portadora de las mutaciones mitocondriales. Por ello, se proponen distintas técnicas de diagnóstico preimplantacional, prenatal o de reproducción asistida a fin de evitar el nacimiento de niños con esta patología. En el presente trabajo se describen y analizan las implicancias científicas y éticas de las nuevas técnicas de reproducción asistida que se proponen a las familias con alto riesgo.Palabras clave: enfermedades mitocondriales, reproducción asistida, trasplante mitocondrial, dignidad humana Ethical value of new reproductive choices in mitochondrial diseasesAbstract: Mitochondrial diseases are a clinically heterogeneous group of disorders with variable clinical features and high morbidity and mortality. As there are different hereditary patterns, complex implications in reproduction are expected; the recurrence risk may be about 25% in autosomal recessive inheritance, 4% in de novo mitochondrial mutations, and an uncertain, but high risk, when the mother is carrier of mitochondrial mutations. Thus, different preimplantation and prenatal diagnosis or assisted reproductive techniques are proposed to avoid the birth of children with these diseases. In this paper scientific and ethical implications of new assisted reproductive techniques offer to high risk families are describe and analyzed. Key words: mitochondrial disorders, assisted reproductive techniques, mitochondrial transplant, human dignity Valoração ética das novas opções reprodutivas nas enfermidades mitocondriaisResumo: As enfermidades mitocondriais são um grupo de desordens clinicamente heterogêneos com manifestações clínicas muito variáveis e alta taxa de morbi-mortalidade. Têm complexas implicações na reprodução, já que os riscos de repetição na família são variáveis, 25% nas formas autossômicas recessivas, ao redor de 4% nos casos de mutações mitocondriais de novo, e um risco incerto porém elevado se a mãe é portadora das mutações mitocondriais. Por isso, se propõem distintas técnicas de diagnóstico pré-implantacional, pré-natal ou de reprodução assistida a fim de evitar o nascimento de crianças com esta patologia. No presente trabalho se descrevem e analisam as implicações científicas e éticas das novas técnicas de reprodução assistida que se propõem às famílias com alto risco.Palavras-chave: enfermidades mitocondriais, reprodução assistida, transplante mitocondrial, dignidade humana

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Risk of developing a mitochondrial DNA deletion disorder

Cited by 188 publications

References 29 publications

Mitochondrial DNA Depletion and Deletions in Paediatric Patients with Neuromuscular Diseases: Novel Phenotypes

Mitochondrial DNA Depletion and Deletions in Paediatric Patients with Neuromuscular Diseases: Novel Phenotypes

Deletion-Mutant mtDNA Increases in Somatic Tissues but Decreases in Female Germ Cells With Age

Valoración ética de las nuevas opciones reproductivas en las enfermedades mitocondriales

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