A Novel Deletion Mutation of Exon 2 of the C19orf12 Gene in an Omani Family with Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN)

Macki, Nabil Al; Rashdi, Ismail Al

doi:10.5001/omj.2017.12

Cited by 5 publications

(3 citation statements)

References 7 publications

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“…On rereading the MRIs of MPAN patients described in the literature, it appears that the hyperintensities described as an eye of the tiger sign are generally intern medullary lamina sign. [28][29][30] In the infratentorial region, the involvement is predominant in the SN and to a lesser extent in the red nuclei. The MRI pattern of iron deposits in AD-MPAN is, therefore, similar to AR-MPAN.…”

Section: Discussionmentioning

confidence: 99%

“…There is no eye of tiger sign, but the typical intern medullary lamina sign is found in five patients of our series, therefore, questioning the true existence of the eye of the tiger sign in MPAN. On re‐reading the MRIs of MPAN patients described in the literature, it appears that the hyperintensities described as an eye of the tiger sign are generally intern medullary lamina sign 28‐30 . In the infratentorial region, the involvement is predominant in the SN and to a lesser extent in the red nuclei.…”

Section: Discussionmentioning

confidence: 99%

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Autosomal Dominant MPAN: Mosaicism Expands the Clinical Spectrum to Atypical Late‐Onset Phenotypes

Angelini,

Durand,

Fergelot

et al. 2023

Movement Disorders

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BackgroundMitochondrial membrane protein‐associated neurodegeneration (MPAN) is caused by mutations in the C19orf12 gene. MPAN typically appears in the first two decades of life and presents with progressive dystonia‐parkinsonism, lower motor neuron signs, optic atrophy, and abnormal iron deposits predominantly in the basal ganglia. MPAN, initially considered as a strictly autosomal recessive disease (AR), turned out to be also dominantly inherited (AD).ObjectivesOur aim was to better characterize the clinical, molecular, and functional spectra associated with such dominant pathogenic heterozygous C19orf12 variants.MethodsWe collected clinical, imaging, and molecular information of eight individuals from four AD‐MPAN families and obtained brain neuropathology results for one. Functional studies, focused on energy and iron metabolism, were conducted on fibroblasts from AD‐MPAN patients, AR‐MPAN patients, and controls.ResultsWe identified four heterozygous C19orf12 variants in eight AD‐MPAN patients. Two of them carrying the familial variant in mosaic displayed an atypical late‐onset phenotype. Fibroblasts from AD‐MPAN showed more severe alterations of iron storage metabolism and autophagy compared to AR‐MPAN cells.ConclusionOur data add strong evidence of the realness of AD‐MPAN with identification of novel monoallelic C19orf12 variants, including at the mosaic state. This has implications in diagnosis procedures. We also expand the phenotypic spectrum of MPAN to late onset atypical presentations. Finally, we demonstrate for the first time more drastic abnormalities of iron metabolism and autophagy in AD‐MPAN than in AR‐MPAN. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Autosomal Dominant MPAN: Mosaicism Expands the Clinical Spectrum to Atypical Late‐Onset Phenotypes

Angelini,

Durand,

Fergelot

et al. 2023

Movement Disorders

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“…The mono or biallelic C19orf12 mutations are cause of this condition. 8,9 The function of C19orf12 remains uncertain, but it may be involved in mitochondrial function, lipid homeostasis, and coenzyme A metabolism. Thus, we have expanded the range of genetic causes associated with MPAN to include C19orf12 mutations.…”

Section: Discussionmentioning

confidence: 99%

A novel p.Ala34Val variant in C19orf12 is associated with neurodegeneration with brain iron accumulation

Kocaaga¹,

Uslu²

2022

NeuroAsia

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Loss-of-function mutations in the C19orf12 gene may lead to mitochondrial membrane protein- associated neurodegeneration (MPAN), which is a subtype of neurodegeneration with brain iron accumulation disorders. It is manifest with juvenile-onset spastic paraparesis, dystonia, dysphagia, optic atrophy, decreased cognitive functions, and neuropsychiatric symptoms. Large amounts of iron are accumulated in the globus pallidus and substantia nigra pars reticulata due to abnormal brain iron metabolism. We report a novel C19orf12 (c.101C>T;p.Ala34Val) homozygous mutation in a Turkish man who presented with postural instability, slow gait and anxiety. Neuroimaging showed mild iron deposition in the basal ganglia and cortical atrophy. These results are consistent with the MPAN. This report demonstrates the importance of testing patients with spastic paraplegia, parkinsonism, motor axonal neuropathy, difficulty walking or dysarthria for MPAN.

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A new NBIA patient from Turkey with homozygous C19ORF12 mutation

et al. 2018

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A Novel Deletion Mutation of Exon 2 of the C19orf12 Gene in an Omani Family with Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN)

Cited by 5 publications

References 7 publications

Autosomal Dominant MPAN: Mosaicism Expands the Clinical Spectrum to Atypical Late‐Onset Phenotypes

Autosomal Dominant MPAN: Mosaicism Expands the Clinical Spectrum to Atypical Late‐Onset Phenotypes

A novel p.Ala34Val variant in C19orf12 is associated with neurodegeneration with brain iron accumulation

A new NBIA patient from Turkey with homozygous C19ORF12 mutation

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