Mutation of the Linker Region of the Polymerase γ-1 (POLG1Gene Associated With Progressive External Ophthalmoplegia and Parkinsonism

Abstract

Objective: To define the molecular basis of the autosomal dominant progressive external ophthalmoplegia and parkinsonism in a large family with a dominantly transmitted multiple mitochondrial DNA deletion disorder.

Levodopa‐Responsive Parkinsonism with Prominent Freezing and Abnormal Dopamine Transporter Scan Associated with SANDO Syndrome

“…One may wonder whether parkinsonism on the background of SANDO syndrome in this and other similar cases was coincidental. This cannot be entirely ruled out; however, the parkinsonism in this case had features similar to other cases of POLG ‐related parkinsonism, including the positive response to the dopaminergic treatment. Another case, compound heterozygous of POLG mutations, but without the full phenotype of SANDO, had both postmortem skeletal muscle biopsy, which was suggestive of mitochondrial myopathy, and brain autopsy showing alpha‐synuclein–defined Lewy bodies in the surviving SN neurones .…”

Levodopa‐Responsive Parkinsonism with Prominent Freezing and Abnormal Dopamine Transporter Scan Associated with SANDO Syndrome

“…One may wonder whether parkinsonism on the background of SANDO syndrome in this and other similar cases was coincidental. This cannot be entirely ruled out; however, the parkinsonism in this case had features similar to other cases of POLG ‐related parkinsonism, including the positive response to the dopaminergic treatment. Another case, compound heterozygous of POLG mutations, but without the full phenotype of SANDO, had both postmortem skeletal muscle biopsy, which was suggestive of mitochondrial myopathy, and brain autopsy showing alpha‐synuclein–defined Lewy bodies in the surviving SN neurones .…”

Selective Neuron Vulnerability in Common and Rare Diseases—Mitochondria in the Focus

“…In line with the high load of mtDNA deletions in SNc dopaminergic neurons of idiopathic PD patients, parkinsonian features were additionally seen in some patients harboring mutations of POLG ( Luoma et al, 2004 ; Hudson et al, 2007 ) and TWNK ( Suomalainen et al, 1997 ; Baloh et al, 2007 ; Kiferle et al, 2013 ). Moreover, mtDNA deletions of idiopathic PD patients were very similar to those found in POLG patients ( Reeve et al, 2008 ).…”

Mitochondrial mimicry of multiple system atrophy of the cerebellar subtype

“…14 POLG1 mutations have been reported in families with PEO, ataxia, and levodopa (L-dopa)-responsive parkinsonism; pathology revealed dopaminergic cell loss in the substantia nigra but not in Lewy bodies. [15][16][17] Our patient has never had a trial of L-dopa. There is no link between common POLG1 mutations and idiopathic Parkinson's disease.…”

Levodopa‐Responsive Parkinsonism with Prominent Freezing and Abnormal Dopamine Transporter Scan Associated with SANDO Syndrome

“…One may wonder whether parkinsonism on the background of SANDO syndrome in this and other similar cases was coincidental. This cannot be entirely ruled out; however, the parkinsonism in this case had features similar to other cases of POLG ‐related parkinsonism, including the positive response to the dopaminergic treatment. Another case, compound heterozygous of POLG mutations, but without the full phenotype of SANDO, had both postmortem skeletal muscle biopsy, which was suggestive of mitochondrial myopathy, and brain autopsy showing alpha‐synuclein–defined Lewy bodies in the surviving SN neurones .…”

Selective Neuron Vulnerability in Common and Rare Diseases—Mitochondria in the Focus

“…In line with the high load of mtDNA deletions in SNc dopaminergic neurons of idiopathic PD patients, parkinsonian features were additionally seen in some patients harboring mutations of POLG ( Luoma et al, 2004 ; Hudson et al, 2007 ) and TWNK ( Suomalainen et al, 1997 ; Baloh et al, 2007 ; Kiferle et al, 2013 ). Moreover, mtDNA deletions of idiopathic PD patients were very similar to those found in POLG patients ( Reeve et al, 2008 ).…”

Mitochondrial mimicry of multiple system atrophy of the cerebellar subtype

“…14 POLG1 mutations have been reported in families with PEO, ataxia, and levodopa (L-dopa)-responsive parkinsonism; pathology revealed dopaminergic cell loss in the substantia nigra but not in Lewy bodies. [15][16][17] Our patient has never had a trial of L-dopa. There is no link between common POLG1 mutations and idiopathic Parkinson's disease.…”

Levodopa‐Responsive Parkinsonism with Prominent Freezing and Abnormal Dopamine Transporter Scan Associated with SANDO Syndrome

“…One may wonder whether parkinsonism on the background of SANDO syndrome in this and other similar cases was coincidental. This cannot be entirely ruled out; however, the parkinsonism in this case had features similar to other cases of POLG ‐related parkinsonism, including the positive response to the dopaminergic treatment. Another case, compound heterozygous of POLG mutations, but without the full phenotype of SANDO, had both postmortem skeletal muscle biopsy, which was suggestive of mitochondrial myopathy, and brain autopsy showing alpha‐synuclein–defined Lewy bodies in the surviving SN neurones .…”

Selective Neuron Vulnerability in Common and Rare Diseases—Mitochondria in the Focus

“…In line with the high load of mtDNA deletions in SNc dopaminergic neurons of idiopathic PD patients, parkinsonian features were additionally seen in some patients harboring mutations of POLG ( Luoma et al, 2004 ; Hudson et al, 2007 ) and TWNK ( Suomalainen et al, 1997 ; Baloh et al, 2007 ; Kiferle et al, 2013 ). Moreover, mtDNA deletions of idiopathic PD patients were very similar to those found in POLG patients ( Reeve et al, 2008 ).…”

Mitochondrial mimicry of multiple system atrophy of the cerebellar subtype

“…14 POLG1 mutations have been reported in families with PEO, ataxia, and levodopa (L-dopa)-responsive parkinsonism; pathology revealed dopaminergic cell loss in the substantia nigra but not in Lewy bodies. [15][16][17] Our patient has never had a trial of L-dopa. There is no link between common POLG1 mutations and idiopathic Parkinson's disease.…”