Transmission of the mitochondrial t8993c mutation in a new family

Hurvitz, Haggit; Naveh, Yaron; Shoseyov, David; Klar, Aharon; Shaag, Avraham; Elpeleg, Orly

doi:10.1002/ajmg.10613

Cited by 6 publications

(3 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To asses phenotypic variability, we examined available clinical data on all reported cases with T8993C mutation and LS using medline database searches [van Erven et al, 1987;de Vries et al, 1993;Santorelli et al, 1994Santorelli et al, , 1996Chakrapani et al, 1998;Fujii et al, 1998Fujii et al, , 2002Suzuki et al, 1998;Vilarinho et al, 2001;Hurvitz et al, 2002;Sciacco et al, 2003;Morava et al, 2006]. Developmental milestones, age at first signs, neurological and ophthalmological status at the last examination, clinical outcome, MRI, and molecular data were reviewed.…”

Section: Review Of the Literaturementioning

confidence: 99%

Long‐term outcome of Leigh syndrome caused by the NARP‐T8993C mtDNA mutation

Debray

Lambert

Lortie

et al. 2007

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Mutations at mitochondrial DNA (mtDNA) nucleotide 8993 can cause neurogenic weakness, ataxia and retinitis pigmentosa (NARP syndrome), or maternally inherited Leigh syndrome (LS), with a correlation between the amount of mutant mtDNA and the severity of the neurological disease. The T8993C mutation is generally considered to be clinically milder than the T8993G mutation but when the level of heteroplasmy exceeds 90%, progressive neurodegeneration has been found. We report on a long-term follow-up of a patient who presented at 4 years of age with typical LS but showed an unexpected resolution of his symptoms and a favorable outcome. At 18 years of age, his neurological examination was near normal, with neither peripheral neuropathy nor retinopathy. mtDNA analysis identified the presence of T8993C mutation at high level (>95%) in the patient's blood leukocytes. This case report and literature review emphasizes the variability of the phenotypic expression of the T8993C mutation and the need for caution in predictive counseling in such patients. (c) 2007 Wiley-Liss, Inc.

show abstract

Section: Review Of the Literaturementioning

confidence: 99%

Long‐term outcome of Leigh syndrome caused by the NARP‐T8993C mtDNA mutation

Debray

Lambert

Lortie

et al. 2007

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…To asses phenotypic variability, we examined available clinical data on all reported cases with T8993C mutation and LS using medline database searches [van Erven et al, 1987; de Vries et al, 1993; Santorelli et al, 1994, 1996; Chakrapani et al, 1998; Fujii et al, 1998, 2002; Suzuki et al, 1998; Vilarinho et al, 2001; Hurvitz et al, 2002; Sciacco et al, 2003; Morava et al, 2006]. Developmental milestones, age at first signs, neurological and ophthalmological status at the last examination, clinical outcome, MRI, and molecular data were reviewed.…”

Section: Methodsmentioning

confidence: 99%

A completely autologous valved conduit prepared in the open form of trileaflets (type VI biovalve): Mold design and valve function in vitro

et al. 2011

View full text Add to dashboard Cite

In-body tissue, architecture technology represents a promising approach for the development of living heart valve replacements and preparation of a series of biovalves. To reduce the degree of regurgitation and increase the orifice ratio, we designed a novel mold for a type VI biovalve. The mold had an outer diameter of 14 mm for implantation in beagles, and it was prepared by assembling two silicone rods with a small aperture (1 mm) between them. One rod had three protrusions of the sinus of Valsalva, whereas the other was almost cylindrical. When the molds were embedded in the subcutaneous pouches of beagles for 1 month, the native connective tissues that subsequently developed covered the entire outer surface of the molds and migrated into the aperture between the rods. The mold from both sides of the harvested cylindrical implant was removed, and homogenous well-balanced trileaflets were found to be separately formed in the open form with a small aperture at the three commissure parts inside the developed conduit, which had a thick homogenous wall even in the sinus of Valsalva. Exposure of the obtained biovalves to physiological aortic valve flow in beagles revealed proper opening motion with a wide orifice area. The closure dynamics were suboptimal, probably due to the reduction in the size of the sinus of Valsalva. The mechanical behavior of this biovalve might allow its use as a living aortic valve replacement.

show abstract

“…This parameter value was set at b = 0.66 based on 87 human mother–offspring pairs (Lott et al ., 1990; Ciafaloni et al ., 1992; Larsson et al ., 1992; Martinuzzi et al ., 1992; Tatuch et al ., 1992; Zhu et al ., 1992; Hammans et al ., 1993, 1995; Piccolo et al ., 1993; Howell et al ., 1994; Santorelli et al ., 1994; Harding et al ., 1995; Houstek et al ., 1995; Makelabengs et al ., 1995; Black et al ., 1996; Mak et al ., 1996; Carelli et al ., 1997; Uziel et al ., 1997; Olsson et al ., 1998; Onishi et al ., 1998; Tanaka et al ., 1998; Chinnery et al ., 1999; White et al ., 1999; Lien et al ., 2001; Porto et al ., 2001; Hurvitz et al ., 2002; Wong et al ., 2002; Kaplanova et al ., 2004; Enns et al ., 2006; Phasukkijwatana et al ., 2006), including the following mutations: m.3243A>G (15 pairs), m.83446A>G (10 pairs), m.11778G>A (23 pairs), m.3460G>A (15 pairs), m.9883T>C (10 pairs) and m.8993T>G (14 pairs). Data from the A3243G mutation taken from blood samples were adjusted to correct for the known decrease in the A3243G mutation level in blood with age (Rajasimha et al ., 2008).…”

Section: Modelling the Inheritance Of Mtdna Heteroplasmymentioning

confidence: 99%

Preventing the transmission of pathogenic mitochondrial DNA mutations: can we achieve long-term benefits from germ-line gene transfer?

2013

View full text Add to dashboard Cite

Mitochondrial medicine is one of the few areas of genetic disease where germ-line transfer is being actively pursued as a treatment option. All of the germ-line transfer methods currently under development involve some carry-over of the maternal mitochondrial DNA (mtDNA) heteroplasmy, potentially delivering the pathogenic mutation to the offspring. Rapid changes in mtDNA heteroplasmy have been observed within a single generation, and so any ‘leakage’ of mutant mtDNA could lead to mtDNA disease in future generations, compromising the reproductive health of the first generation, and leading to repeated interventions in subsequent generations. To determine whether this is a real concern, we developed a model of mtDNA heteroplasmy inheritance by studying 87 mother–child pairs, and predicted the likely outcome of different levels of ‘mutant mtDNA leakage’ on subsequent maternal generations. This showed that, for a clinical threshold of 60%, reducing the proportion of mutant mtDNA to <5% dramatically reduces the chance of disease recurrence in subsequent generations, but transmitting >5% mutant mtDNA was associated with a significant chance of disease recurrence. Mutations with a lower clinical threshold were associated with a higher risk of recurrence. Our findings provide reassurance that, at least from an mtDNA perspective, methods currently under development have the potential to effectively eradicate pathogenic mtDNA mutations from subsequent generations.

show abstract

Transmission of the mitochondrial t8993c mutation in a new family

Cited by 6 publications

References 8 publications

Long‐term outcome of Leigh syndrome caused by the NARP‐T8993C mtDNA mutation

Long‐term outcome of Leigh syndrome caused by the NARP‐T8993C mtDNA mutation

A completely autologous valved conduit prepared in the open form of trileaflets (type VI biovalve): Mold design and valve function in vitro

Preventing the transmission of pathogenic mitochondrial DNA mutations: can we achieve long-term benefits from germ-line gene transfer?

Contact Info

Product

Resources

About