Research ExplorerPublicationsMutations in COX7B cause microphthalmia with linear skin les...

Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease.

Standard

Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease. / Indrieri, Alessia; van Rahden, Vanessa; Alexandra, Vanessa; Tiranti, Valeria; Morleo, Manuela; Iaconis, Daniela; Tammaro, Roberta; D'Amato, Ilaria; Conte, Ivan; Maystadt, Isabelle; Demuth, Stephanie; Kutsche, Kerstin; Kutsche, Kerstin; Zeviani, Massimo; Franco, Brunella.

In: AM J HUM GENET, Vol. 91, No. 5, 5, 2012, p. 942-949.

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

Harvard

Indrieri, A, van Rahden, V, Alexandra, V, Tiranti, V, Morleo, M, Iaconis, D, Tammaro, R, D'Amato, I, Conte, I, Maystadt, I, Demuth, S, Kutsche, K, Kutsche, K, Zeviani, M & Franco, B 2012, 'Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease.', AM J HUM GENET, vol. 91, no. 5, 5, pp. 942-949. <http://www.ncbi.nlm.nih.gov/pubmed/23122588?dopt=Citation>

APA

Indrieri, A., van Rahden, V., Alexandra, V., Tiranti, V., Morleo, M., Iaconis, D., Tammaro, R., D'Amato, I., Conte, I., Maystadt, I., Demuth, S., Kutsche, K., Kutsche, K., Zeviani, M., & Franco, B. (2012). Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease. AM J HUM GENET, 91(5), 942-949. [5]. http://www.ncbi.nlm.nih.gov/pubmed/23122588?dopt=Citation

Vancouver

Indrieri A, van Rahden V, Alexandra V, Tiranti V, Morleo M, Iaconis D et al. Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease. AM J HUM GENET. 2012;91(5):942-949. 5.

Bibtex

@article{8413b169e57d4c1181ba69c2bef9685b,
title = "Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease.",
abstract = "Microphthalmia with linear skin lesions (MLS) is an X-linked dominant male-lethal disorder associated with mutations in holocytochrome c-type synthase (HCCS), which encodes a crucial player of the mitochondrial respiratory chain (MRC). Unlike other mitochondrial diseases, MLS is characterized by a well-recognizable neurodevelopmental phenotype. Interestingly, not all clinically diagnosed MLS cases have mutations in HCCS, thus suggesting genetic heterogeneity for this disorder. Among the possible candidates, we analyzed the X-linked COX7B and found deleterious de novo mutations in two simplex cases and a nonsense mutation, which segregates with the disease, in a familial case. COX7B encodes a poorly characterized structural subunit of cytochrome c oxidase (COX), the MRC complex IV. We demonstrated that COX7B is indispensable for COX assembly, COX activity, and mitochondrial respiration. Downregulation of the COX7B ortholog (cox7B) in medaka (Oryzias latipes) resulted in microcephaly and microphthalmia that recapitulated the MLS phenotype and demonstrated an essential function of complex IV activity in vertebrate CNS development. Our results indicate an evolutionary conserved role of the MRC complexes III and IV for the proper development of the CNS in vertebrates and uncover a group of mitochondrial diseases hallmarked by a developmental phenotype.",
keywords = "Animals, Humans, Female, Gene Expression Regulation, Genotype, Phenotype, Amino Acid Sequence, Molecular Sequence Data, Base Sequence, Pedigree, Amino Acid Substitution, Cell Line, Skin/pathology, *Mutation, Electron Transport Complex IV/*genetics, Genes, X-Linked, Lyases/genetics, Microphthalmos/*genetics/metabolism/pathology, Mitochondrial Diseases/*genetics/metabolism/pathology, Oryzias/genetics/metabolism, Animals, Humans, Female, Gene Expression Regulation, Genotype, Phenotype, Amino Acid Sequence, Molecular Sequence Data, Base Sequence, Pedigree, Amino Acid Substitution, Cell Line, Skin/pathology, *Mutation, Electron Transport Complex IV/*genetics, Genes, X-Linked, Lyases/genetics, Microphthalmos/*genetics/metabolism/pathology, Mitochondrial Diseases/*genetics/metabolism/pathology, Oryzias/genetics/metabolism",
author = "Alessia Indrieri and {van Rahden}, Vanessa and Vanessa Alexandra and Valeria Tiranti and Manuela Morleo and Daniela Iaconis and Roberta Tammaro and Ilaria D'Amato and Ivan Conte and Isabelle Maystadt and Stephanie Demuth and Kerstin Kutsche and Kerstin Kutsche and Massimo Zeviani and Brunella Franco",
year = "2012",
language = "English",
volume = "91",
pages = "942--949",
journal = "AM J HUM GENET",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease.

AU - Indrieri, Alessia

AU - van Rahden, Vanessa

AU - Alexandra, Vanessa

AU - Tiranti, Valeria

AU - Morleo, Manuela

AU - Iaconis, Daniela

AU - Tammaro, Roberta

AU - D'Amato, Ilaria

AU - Conte, Ivan

AU - Maystadt, Isabelle

AU - Demuth, Stephanie

AU - Kutsche, Kerstin

AU - Kutsche, Kerstin

AU - Zeviani, Massimo

AU - Franco, Brunella

PY - 2012

Y1 - 2012

N2 - Microphthalmia with linear skin lesions (MLS) is an X-linked dominant male-lethal disorder associated with mutations in holocytochrome c-type synthase (HCCS), which encodes a crucial player of the mitochondrial respiratory chain (MRC). Unlike other mitochondrial diseases, MLS is characterized by a well-recognizable neurodevelopmental phenotype. Interestingly, not all clinically diagnosed MLS cases have mutations in HCCS, thus suggesting genetic heterogeneity for this disorder. Among the possible candidates, we analyzed the X-linked COX7B and found deleterious de novo mutations in two simplex cases and a nonsense mutation, which segregates with the disease, in a familial case. COX7B encodes a poorly characterized structural subunit of cytochrome c oxidase (COX), the MRC complex IV. We demonstrated that COX7B is indispensable for COX assembly, COX activity, and mitochondrial respiration. Downregulation of the COX7B ortholog (cox7B) in medaka (Oryzias latipes) resulted in microcephaly and microphthalmia that recapitulated the MLS phenotype and demonstrated an essential function of complex IV activity in vertebrate CNS development. Our results indicate an evolutionary conserved role of the MRC complexes III and IV for the proper development of the CNS in vertebrates and uncover a group of mitochondrial diseases hallmarked by a developmental phenotype.

AB - Microphthalmia with linear skin lesions (MLS) is an X-linked dominant male-lethal disorder associated with mutations in holocytochrome c-type synthase (HCCS), which encodes a crucial player of the mitochondrial respiratory chain (MRC). Unlike other mitochondrial diseases, MLS is characterized by a well-recognizable neurodevelopmental phenotype. Interestingly, not all clinically diagnosed MLS cases have mutations in HCCS, thus suggesting genetic heterogeneity for this disorder. Among the possible candidates, we analyzed the X-linked COX7B and found deleterious de novo mutations in two simplex cases and a nonsense mutation, which segregates with the disease, in a familial case. COX7B encodes a poorly characterized structural subunit of cytochrome c oxidase (COX), the MRC complex IV. We demonstrated that COX7B is indispensable for COX assembly, COX activity, and mitochondrial respiration. Downregulation of the COX7B ortholog (cox7B) in medaka (Oryzias latipes) resulted in microcephaly and microphthalmia that recapitulated the MLS phenotype and demonstrated an essential function of complex IV activity in vertebrate CNS development. Our results indicate an evolutionary conserved role of the MRC complexes III and IV for the proper development of the CNS in vertebrates and uncover a group of mitochondrial diseases hallmarked by a developmental phenotype.

KW - Animals

KW - Humans

KW - Female

KW - Gene Expression Regulation

KW - Genotype

KW - Phenotype

KW - Amino Acid Sequence

KW - Molecular Sequence Data

KW - Base Sequence

KW - Pedigree

KW - Amino Acid Substitution

KW - Cell Line

KW - Skin/pathology

KW - Mutation

KW - Electron Transport Complex IV/genetics

KW - Genes, X-Linked

KW - Lyases/genetics

KW - Microphthalmos/genetics/metabolism/pathology

KW - Mitochondrial Diseases/genetics/metabolism/pathology

KW - Oryzias/genetics/metabolism

KW - Animals

KW - Humans

KW - Female

KW - Gene Expression Regulation

KW - Genotype

KW - Phenotype

KW - Amino Acid Sequence

KW - Molecular Sequence Data

KW - Base Sequence

KW - Pedigree

KW - Amino Acid Substitution

KW - Cell Line

KW - Skin/pathology

KW - Mutation

KW - Electron Transport Complex IV/genetics

KW - Genes, X-Linked

KW - Lyases/genetics

KW - Microphthalmos/genetics/metabolism/pathology

KW - Mitochondrial Diseases/genetics/metabolism/pathology

KW - Oryzias/genetics/metabolism

M3 - SCORING: Journal article

VL - 91

SP - 942

EP - 949

JO - AM J HUM GENET

JF - AM J HUM GENET

SN - 0002-9297

IS - 5

M1 - 5

ER -