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Two Cockayne Syndrome patients with a novel splice site mutation – clinical and metabolic analyses

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Two Cockayne Syndrome patients with a novel splice site mutation – clinical and metabolic analyses. / Sanchez-Roman, Ines; Lautrup, Sofie; Aamann, Maria Diget; Neilan, Edward G.; Østergaard, John R.; Stevnsner, Tinna.

I: Mechanisms of Ageing and Development, Bind 175, 10.2018, s. 7-16.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Sanchez-Roman, I, Lautrup, S, Aamann, MD, Neilan, EG, Østergaard, JR & Stevnsner, T 2018, 'Two Cockayne Syndrome patients with a novel splice site mutation – clinical and metabolic analyses', Mechanisms of Ageing and Development, bind 175, s. 7-16. https://doi.org/10.1016/j.mad.2018.06.001

APA

Sanchez-Roman, I., Lautrup, S., Aamann, M. D., Neilan, E. G., Østergaard, J. R., & Stevnsner, T. (2018). Two Cockayne Syndrome patients with a novel splice site mutation – clinical and metabolic analyses. Mechanisms of Ageing and Development, 175, 7-16. https://doi.org/10.1016/j.mad.2018.06.001

CBE

MLA

Vancouver

Author

Sanchez-Roman, Ines ; Lautrup, Sofie ; Aamann, Maria Diget ; Neilan, Edward G. ; Østergaard, John R. ; Stevnsner, Tinna. / Two Cockayne Syndrome patients with a novel splice site mutation – clinical and metabolic analyses. I: Mechanisms of Ageing and Development. 2018 ; Bind 175. s. 7-16.

Bibtex

@article{5c40550365d14ff5a5c08db467385833,
title = "Two Cockayne Syndrome patients with a novel splice site mutation – clinical and metabolic analyses",
abstract = "Cockayne Syndrome (CS) is a rare autosomal recessive disorder, which leads to neurodegeneration, growth failure and premature aging. Most of the cases are due to mutations in the ERCC6 gene, which encodes the protein CSB. CSB is involved in several functions including DNA repair and transcription. Here we describe two Danish brothers with CS. Both patients carried a novel splice site mutation (c.2382+2T>G), and a previously described nonsense mutation (c.3259C>T, p.Arg1087X) in a biallelic state. Both patients presented the cardinal features of the disease including microcephaly, congenital cataract and postnatal growth failure. In addition, their fibroblasts were hypersensitive to UV irradiation and exhibited increased superoxide levels in comparison to fibroblasts from healthy age and gender matched individuals. Metabolomic analysis revealed a distinctive metabolic profile in cells from the CS patients compared to control cells. Among others, α-ketoglutarate, hydroxyglutarate and certain amino acids (ornithine, proline and glycine) were reduced in the CS patient fibroblasts, whereas glycolytic intermediates (glucose-6-phosphate and pyruvic acid) and fatty acids (palmitic, stearic and myristic acid) were increased. Our data not only provide additional information to the database of CS mutations, but also point towards targets for potential treatment of this devastating disease.",
keywords = "Cockayne Syndrome, CSB, ERCC6, Metabolomics, Premature aging, Splice site mutation",
author = "Ines Sanchez-Roman and Sofie Lautrup and Aamann, {Maria Diget} and Neilan, {Edward G.} and {\O}stergaard, {John R.} and Tinna Stevnsner",
year = "2018",
month = oct,
doi = "10.1016/j.mad.2018.06.001",
language = "English",
volume = "175",
pages = "7--16",
journal = "Mechanisms of Ageing and Development",
issn = "0047-6374",
publisher = "Elsevier Ireland Ltd.",

}

RIS

TY - JOUR

T1 - Two Cockayne Syndrome patients with a novel splice site mutation – clinical and metabolic analyses

AU - Sanchez-Roman, Ines

AU - Lautrup, Sofie

AU - Aamann, Maria Diget

AU - Neilan, Edward G.

AU - Østergaard, John R.

AU - Stevnsner, Tinna

PY - 2018/10

Y1 - 2018/10

N2 - Cockayne Syndrome (CS) is a rare autosomal recessive disorder, which leads to neurodegeneration, growth failure and premature aging. Most of the cases are due to mutations in the ERCC6 gene, which encodes the protein CSB. CSB is involved in several functions including DNA repair and transcription. Here we describe two Danish brothers with CS. Both patients carried a novel splice site mutation (c.2382+2T>G), and a previously described nonsense mutation (c.3259C>T, p.Arg1087X) in a biallelic state. Both patients presented the cardinal features of the disease including microcephaly, congenital cataract and postnatal growth failure. In addition, their fibroblasts were hypersensitive to UV irradiation and exhibited increased superoxide levels in comparison to fibroblasts from healthy age and gender matched individuals. Metabolomic analysis revealed a distinctive metabolic profile in cells from the CS patients compared to control cells. Among others, α-ketoglutarate, hydroxyglutarate and certain amino acids (ornithine, proline and glycine) were reduced in the CS patient fibroblasts, whereas glycolytic intermediates (glucose-6-phosphate and pyruvic acid) and fatty acids (palmitic, stearic and myristic acid) were increased. Our data not only provide additional information to the database of CS mutations, but also point towards targets for potential treatment of this devastating disease.

AB - Cockayne Syndrome (CS) is a rare autosomal recessive disorder, which leads to neurodegeneration, growth failure and premature aging. Most of the cases are due to mutations in the ERCC6 gene, which encodes the protein CSB. CSB is involved in several functions including DNA repair and transcription. Here we describe two Danish brothers with CS. Both patients carried a novel splice site mutation (c.2382+2T>G), and a previously described nonsense mutation (c.3259C>T, p.Arg1087X) in a biallelic state. Both patients presented the cardinal features of the disease including microcephaly, congenital cataract and postnatal growth failure. In addition, their fibroblasts were hypersensitive to UV irradiation and exhibited increased superoxide levels in comparison to fibroblasts from healthy age and gender matched individuals. Metabolomic analysis revealed a distinctive metabolic profile in cells from the CS patients compared to control cells. Among others, α-ketoglutarate, hydroxyglutarate and certain amino acids (ornithine, proline and glycine) were reduced in the CS patient fibroblasts, whereas glycolytic intermediates (glucose-6-phosphate and pyruvic acid) and fatty acids (palmitic, stearic and myristic acid) were increased. Our data not only provide additional information to the database of CS mutations, but also point towards targets for potential treatment of this devastating disease.

KW - Cockayne Syndrome

KW - CSB

KW - ERCC6

KW - Metabolomics

KW - Premature aging

KW - Splice site mutation

UR - http://www.scopus.com/inward/record.url?scp=85049490878&partnerID=8YFLogxK

U2 - 10.1016/j.mad.2018.06.001

DO - 10.1016/j.mad.2018.06.001

M3 - Journal article

C2 - 29944916

AN - SCOPUS:85049490878

VL - 175

SP - 7

EP - 16

JO - Mechanisms of Ageing and Development

JF - Mechanisms of Ageing and Development

SN - 0047-6374

ER -