Novel Mitochondrial DNA ND5 Mutation in a Patient With Clinical Features of MELAS and MERRF

Abstract

Background: The mitochondrial DNA gene encoding subunit 5 of complex I (ND5) has turned out to be a hot spot for mutations associated with mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes (MELAS) and various overlap syndromes. Objective: To describe a novel mutation in the ND5 gene in a young man man with an overlap syndrome of MELAS and myoclonus epilepsy with ragged-red fibers.

Mitochondrial encephalopathy in a patient with a 13042G>A de novo mutation

“…This gene may be a hot spot for mutations in several overlap syndromes, including symptoms and signs of MELAS, MERRF , Leber's hereditary optic neuropathy (LHON) and Leigh syndromes. The case presented here corresponds with those described by Naini et al ,1 although it resembles MERRF rather than MELAS (only MRI hyperintensities and abnormal lactic acid curve). Valentino et al 5 also did not find typical ragged red fibres but a decrease in complex I activity was observed.…”

“…Mitochondrial DNA point mutations are associated with various syndromes, among which mitochondrial myopathy, encephalopathy, lactic acidosis and stroke (MELAS) and myoclonic epilepsy with ragged red fibres (MERRF) are the most common 1. Here we present a case report of a young man with a mitochondrial encephalomyopathy caused by a mutation in the ND5 gene (13042A>G), which has been described previously 1…”

Mitochondrial encephalopathy in a patient with a 13042G>A de novo mutation

“…This gene may be a hot spot for mutations in several overlap syndromes, including symptoms and signs of MELAS, MERRF , Leber's hereditary optic neuropathy (LHON) and Leigh syndromes. The case presented here corresponds with those described by Naini et al ,1 although it resembles MERRF rather than MELAS (only MRI hyperintensities and abnormal lactic acid curve). Valentino et al 5 also did not find typical ragged red fibres but a decrease in complex I activity was observed.…”

“…Mitochondrial DNA point mutations are associated with various syndromes, among which mitochondrial myopathy, encephalopathy, lactic acidosis and stroke (MELAS) and myoclonic epilepsy with ragged red fibres (MERRF) are the most common 1. Here we present a case report of a young man with a mitochondrial encephalomyopathy caused by a mutation in the ND5 gene (13042A>G), which has been described previously 1…”

Mitochondrial DNA Pathogenic Variants in Ophthalmic Diseases: A Review

“…Several subsequent studies have corroborated the role of mitochondrial abnormalities in glaucoma in different populations [ 76 , 77 , 78 , 79 , 80 ]. Likewise, a similar clustering of mitochondrial variants in Complex I has also been observed in other optic neuropathies like LHON [ 15 ] and mitochondrial disorders like MERRF and MELAS [ 81 ]. Furthermore, Collins and colleagues have identified several mtDNA pathogenic variants with POAG in African Americans, including m.6150G>A, m.6253C>T, and m.6480G>A in MT-CO1 , and m.2220A>G in MT-RNR2 associated.…”

Changing phenotypic expression in a patient with a mitochondrial encephalopathy due to 13042G>A de novo mutation—a 5 year follow up

“…Recently, there has been increased interest in the DNA gene encoding subunit 5 of complex I (MT-ND5), as a mutation hot spot for several overlap syndromes (Blok et al 2007 ). Although13042G>A mutation was described earlier by Naini et al ( 2005 ), we present a patient with a de novo mutation and long-term follow-up. This long-term observation shows the very complex pattern of neurological abnormalities evolving during 5 years from epilepsy, myoclonus and dystonia to choreatic movements with ophtalmoplegia and optic neuropathy.…”

Mitochondrial encephalopathy in a patient with a 13042G>A de novo mutation

“…This gene may be a hot spot for mutations in several overlap syndromes, including symptoms and signs of MELAS, MERRF , Leber's hereditary optic neuropathy (LHON) and Leigh syndromes. The case presented here corresponds with those described by Naini et al ,1 although it resembles MERRF rather than MELAS (only MRI hyperintensities and abnormal lactic acid curve). Valentino et al 5 also did not find typical ragged red fibres but a decrease in complex I activity was observed.…”

“…Mitochondrial DNA point mutations are associated with various syndromes, among which mitochondrial myopathy, encephalopathy, lactic acidosis and stroke (MELAS) and myoclonic epilepsy with ragged red fibres (MERRF) are the most common 1. Here we present a case report of a young man with a mitochondrial encephalomyopathy caused by a mutation in the ND5 gene (13042A>G), which has been described previously 1…”

Mitochondrial DNA Pathogenic Variants in Ophthalmic Diseases: A Review

“…Several subsequent studies have corroborated the role of mitochondrial abnormalities in glaucoma in different populations [ 76 , 77 , 78 , 79 , 80 ]. Likewise, a similar clustering of mitochondrial variants in Complex I has also been observed in other optic neuropathies like LHON [ 15 ] and mitochondrial disorders like MERRF and MELAS [ 81 ]. Furthermore, Collins and colleagues have identified several mtDNA pathogenic variants with POAG in African Americans, including m.6150G>A, m.6253C>T, and m.6480G>A in MT-CO1 , and m.2220A>G in MT-RNR2 associated.…”

Changing phenotypic expression in a patient with a mitochondrial encephalopathy due to 13042G>A de novo mutation—a 5 year follow up

“…Recently, there has been increased interest in the DNA gene encoding subunit 5 of complex I (MT-ND5), as a mutation hot spot for several overlap syndromes (Blok et al 2007 ). Although13042G>A mutation was described earlier by Naini et al ( 2005 ), we present a patient with a de novo mutation and long-term follow-up. This long-term observation shows the very complex pattern of neurological abnormalities evolving during 5 years from epilepsy, myoclonus and dystonia to choreatic movements with ophtalmoplegia and optic neuropathy.…”

Mitochondrial encephalopathy in a patient with a 13042G>A de novo mutation

“…This gene may be a hot spot for mutations in several overlap syndromes, including symptoms and signs of MELAS, MERRF , Leber's hereditary optic neuropathy (LHON) and Leigh syndromes. The case presented here corresponds with those described by Naini et al ,1 although it resembles MERRF rather than MELAS (only MRI hyperintensities and abnormal lactic acid curve). Valentino et al 5 also did not find typical ragged red fibres but a decrease in complex I activity was observed.…”

“…Mitochondrial DNA point mutations are associated with various syndromes, among which mitochondrial myopathy, encephalopathy, lactic acidosis and stroke (MELAS) and myoclonic epilepsy with ragged red fibres (MERRF) are the most common 1. Here we present a case report of a young man with a mitochondrial encephalomyopathy caused by a mutation in the ND5 gene (13042A>G), which has been described previously 1…”

Mitochondrial DNA Pathogenic Variants in Ophthalmic Diseases: A Review

“…Several subsequent studies have corroborated the role of mitochondrial abnormalities in glaucoma in different populations [ 76 , 77 , 78 , 79 , 80 ]. Likewise, a similar clustering of mitochondrial variants in Complex I has also been observed in other optic neuropathies like LHON [ 15 ] and mitochondrial disorders like MERRF and MELAS [ 81 ]. Furthermore, Collins and colleagues have identified several mtDNA pathogenic variants with POAG in African Americans, including m.6150G>A, m.6253C>T, and m.6480G>A in MT-CO1 , and m.2220A>G in MT-RNR2 associated.…”

Changing phenotypic expression in a patient with a mitochondrial encephalopathy due to 13042G>A de novo mutation—a 5 year follow up

“…Recently, there has been increased interest in the DNA gene encoding subunit 5 of complex I (MT-ND5), as a mutation hot spot for several overlap syndromes (Blok et al 2007 ). Although13042G>A mutation was described earlier by Naini et al ( 2005 ), we present a patient with a de novo mutation and long-term follow-up. This long-term observation shows the very complex pattern of neurological abnormalities evolving during 5 years from epilepsy, myoclonus and dystonia to choreatic movements with ophtalmoplegia and optic neuropathy.…”