RT Journal Article
T1 Two Cockayne Syndrome patients with a novel splice site mutation – clinical and metabolic analyses
A1 Sánchez-Román Rojas, Inés
A1 Lautrup, Sofie
A1 Aamann, Maria Diget
A1 Neilan, Edward
A1 Østergaard, John
A1 Stevnsner, Tinna
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.
PB Elsevier
SN 0047-6374
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/96759
UL https://hdl.handle.net/20.500.14352/96759
LA eng
NO Sanchez-Roman, Ines, et al. «Two Cockayne Syndrome Patients with a Novel Splice Site Mutation – Clinical and Metabolic Analyses». Mechanisms of Ageing and Development, vol. 175, octubre de 2018, pp. 7-16. https://doi.org/10.1016/j.mad.2018.06.001.
NO This work was supported by the VELUX Foundation, the Danish Research Council and the NovoNordic Foundation.
NO VELUX Foundation
NO Danish Research Council
NO NovoNordic Foundation
DS Docta Complutense
RD 6 abr 2025