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Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation

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Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. / Hartig, Monika B; Iuso, Arcangela; Haack, Tobias; Kmiec, Tomasz; Jurkiewicz, Elzbieta; Heim, Katharina; Roeber, Sigrun; Tarabin, Victoria; Dusi, Sabrina; Krajewska-Walasek, Malgorzata; Jozwiak, Sergiusz; Hempel, Maja; Winkelmann, Juliane; Elstner, Matthias; Oexle, Konrad; Klopstock, Thomas; Mueller-Felber, Wolfgang; Gasser, Thomas; Trenkwalder, Claudia; Tiranti, Valeria; Kretzschmar, Hans; Schmitz, Gerd; Strom, Tim M; Meitinger, Thomas; Prokisch, Holger.

In: AM J HUM GENET, Vol. 89, No. 4, 07.10.2011, p. 543-50.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hartig, MB, Iuso, A, Haack, T, Kmiec, T, Jurkiewicz, E, Heim, K, Roeber, S, Tarabin, V, Dusi, S, Krajewska-Walasek, M, Jozwiak, S, Hempel, M, Winkelmann, J, Elstner, M, Oexle, K, Klopstock, T, Mueller-Felber, W, Gasser, T, Trenkwalder, C, Tiranti, V, Kretzschmar, H, Schmitz, G, Strom, TM, Meitinger, T & Prokisch, H 2011, 'Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation', AM J HUM GENET, vol. 89, no. 4, pp. 543-50. https://doi.org/10.1016/j.ajhg.2011.09.007

APA

Hartig, M. B., Iuso, A., Haack, T., Kmiec, T., Jurkiewicz, E., Heim, K., Roeber, S., Tarabin, V., Dusi, S., Krajewska-Walasek, M., Jozwiak, S., Hempel, M., Winkelmann, J., Elstner, M., Oexle, K., Klopstock, T., Mueller-Felber, W., Gasser, T., Trenkwalder, C., ... Prokisch, H. (2011). Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. AM J HUM GENET, 89(4), 543-50. https://doi.org/10.1016/j.ajhg.2011.09.007

Vancouver

Hartig MB, Iuso A, Haack T, Kmiec T, Jurkiewicz E, Heim K et al. Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. AM J HUM GENET. 2011 Oct 7;89(4):543-50. https://doi.org/10.1016/j.ajhg.2011.09.007

Bibtex

@article{903f2f9348b64a25996e6ce227d32cdb,
title = "Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation",
abstract = "The disease classification neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of progressive neurodegenerative disorders characterized by brain iron deposits in the basal ganglia. For about half of the cases, the molecular basis is currently unknown. We used homozygosity mapping followed by candidate gene sequencing to identify a homozygous 11 bp deletion in the orphan gene C19orf12. Mutation screening of 23 ideopathic NBIA index cases revealed two mutated alleles in 18 of them, and one loss-of-function mutation is the most prevalent. We also identified compound heterozygous missense mutations in a case initially diagnosed with Parkinson disease at age 49. Psychiatric signs, optic atrophy, and motor axonal neuropathy were common findings. Compared to the most prevalent NBIA subtype, pantothenate kinase associated neurodegeneration (PKAN), individuals with two C19orf12 mutations were older at age of onset and the disease progressed more slowly. A polyclonal antibody against the predicted membrane spanning protein showed a mitochondrial localization. A histopathological examination in a single autopsy case detected Lewy bodies, tangles, spheroids, and tau pathology. The mitochondrial localization together with the immunohistopathological findings suggests a pathomechanistic overlap with common forms of neurodegenerative disorders.",
keywords = "Adolescent, Adult, Amino Acid Sequence, Brain, Case-Control Studies, Child, Child, Preschool, Cloning, Molecular, Cohort Studies, Female, Heterozygote, Homozygote, Humans, Iron, Male, Mitochondria, Mitochondrial Proteins, Molecular Sequence Data, Mutation, Mutation, Missense, Neurodegenerative Diseases, Pedigree, Sequence Homology, Amino Acid",
author = "Hartig, {Monika B} and Arcangela Iuso and Tobias Haack and Tomasz Kmiec and Elzbieta Jurkiewicz and Katharina Heim and Sigrun Roeber and Victoria Tarabin and Sabrina Dusi and Malgorzata Krajewska-Walasek and Sergiusz Jozwiak and Maja Hempel and Juliane Winkelmann and Matthias Elstner and Konrad Oexle and Thomas Klopstock and Wolfgang Mueller-Felber and Thomas Gasser and Claudia Trenkwalder and Valeria Tiranti and Hans Kretzschmar and Gerd Schmitz and Strom, {Tim M} and Thomas Meitinger and Holger Prokisch",
note = "Copyright {\textcopyright} 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.",
year = "2011",
month = oct,
day = "7",
doi = "10.1016/j.ajhg.2011.09.007",
language = "English",
volume = "89",
pages = "543--50",
journal = "AM J HUM GENET",
issn = "0002-9297",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation

AU - Hartig, Monika B

AU - Iuso, Arcangela

AU - Haack, Tobias

AU - Kmiec, Tomasz

AU - Jurkiewicz, Elzbieta

AU - Heim, Katharina

AU - Roeber, Sigrun

AU - Tarabin, Victoria

AU - Dusi, Sabrina

AU - Krajewska-Walasek, Malgorzata

AU - Jozwiak, Sergiusz

AU - Hempel, Maja

AU - Winkelmann, Juliane

AU - Elstner, Matthias

AU - Oexle, Konrad

AU - Klopstock, Thomas

AU - Mueller-Felber, Wolfgang

AU - Gasser, Thomas

AU - Trenkwalder, Claudia

AU - Tiranti, Valeria

AU - Kretzschmar, Hans

AU - Schmitz, Gerd

AU - Strom, Tim M

AU - Meitinger, Thomas

AU - Prokisch, Holger

N1 - Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

PY - 2011/10/7

Y1 - 2011/10/7

N2 - The disease classification neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of progressive neurodegenerative disorders characterized by brain iron deposits in the basal ganglia. For about half of the cases, the molecular basis is currently unknown. We used homozygosity mapping followed by candidate gene sequencing to identify a homozygous 11 bp deletion in the orphan gene C19orf12. Mutation screening of 23 ideopathic NBIA index cases revealed two mutated alleles in 18 of them, and one loss-of-function mutation is the most prevalent. We also identified compound heterozygous missense mutations in a case initially diagnosed with Parkinson disease at age 49. Psychiatric signs, optic atrophy, and motor axonal neuropathy were common findings. Compared to the most prevalent NBIA subtype, pantothenate kinase associated neurodegeneration (PKAN), individuals with two C19orf12 mutations were older at age of onset and the disease progressed more slowly. A polyclonal antibody against the predicted membrane spanning protein showed a mitochondrial localization. A histopathological examination in a single autopsy case detected Lewy bodies, tangles, spheroids, and tau pathology. The mitochondrial localization together with the immunohistopathological findings suggests a pathomechanistic overlap with common forms of neurodegenerative disorders.

AB - The disease classification neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of progressive neurodegenerative disorders characterized by brain iron deposits in the basal ganglia. For about half of the cases, the molecular basis is currently unknown. We used homozygosity mapping followed by candidate gene sequencing to identify a homozygous 11 bp deletion in the orphan gene C19orf12. Mutation screening of 23 ideopathic NBIA index cases revealed two mutated alleles in 18 of them, and one loss-of-function mutation is the most prevalent. We also identified compound heterozygous missense mutations in a case initially diagnosed with Parkinson disease at age 49. Psychiatric signs, optic atrophy, and motor axonal neuropathy were common findings. Compared to the most prevalent NBIA subtype, pantothenate kinase associated neurodegeneration (PKAN), individuals with two C19orf12 mutations were older at age of onset and the disease progressed more slowly. A polyclonal antibody against the predicted membrane spanning protein showed a mitochondrial localization. A histopathological examination in a single autopsy case detected Lewy bodies, tangles, spheroids, and tau pathology. The mitochondrial localization together with the immunohistopathological findings suggests a pathomechanistic overlap with common forms of neurodegenerative disorders.

KW - Adolescent

KW - Adult

KW - Amino Acid Sequence

KW - Brain

KW - Case-Control Studies

KW - Child

KW - Child, Preschool

KW - Cloning, Molecular

KW - Cohort Studies

KW - Female

KW - Heterozygote

KW - Homozygote

KW - Humans

KW - Iron

KW - Male

KW - Mitochondria

KW - Mitochondrial Proteins

KW - Molecular Sequence Data

KW - Mutation

KW - Mutation, Missense

KW - Neurodegenerative Diseases

KW - Pedigree

KW - Sequence Homology, Amino Acid

U2 - 10.1016/j.ajhg.2011.09.007

DO - 10.1016/j.ajhg.2011.09.007

M3 - SCORING: Journal article

C2 - 21981780

VL - 89

SP - 543

EP - 550

JO - AM J HUM GENET

JF - AM J HUM GENET

SN - 0002-9297

IS - 4

ER -