Expansion of the clinical and molecular spectrum of an XPD-related disorder linked to biallelic mutations in ERCC2 gene.
DNA repair-deficiency disorder
ERCC2
XPD
pilocytic astrocytoma
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
05
03
2021
received:
17
11
2020
accepted:
10
03
2021
pubmed:
19
3
2021
medline:
19
2
2022
entrez:
18
3
2021
Statut:
ppublish
Résumé
Bi-allelic inactivation of XPD protein, a nucleotide excision repair (NER) signaling pathway component encoded by ERCC2 gene, has been associated with several defective DNA repair phenotypes, including xeroderma pigmentosum, photosensitive trichothiodystrophy, and cerebro-oculo-facio-skeletal syndrome. We report a pediatric patient harboring two compound heterozygous variants in ERCC2 gene, c.361-1G>A and c.2125A>C (p.Thr709Pro), affected by severe postnatal growth deficiency, microcephaly, facial dysmorphisms and pilocytic astrocytoma of the brainstem. Some of these features point to a DNA repair syndrome, and altogether delineate a phenotype differentiating from disorders known to be associated with ERCC2 mutations. The DNA repair efficiency following UV irradiation in the proband's skin fibroblasts was defective indicating that the new set of ERCC2 alleles impacts on NER efficiency. Sequencing analysis on tumor DNA did not reveal any somatic deleterious point variant in cancer-related genes, while SNP-array analysis disclosed a 2 Mb microduplication involving the 7q34 region, spanning from KIAA1549 to BRAF, and resulting in the KIAA1549:BRAF fusion protein, a marker of pilocytic astrocytoma. In conclusion, this report expands the clinical and mutational spectrum of ERCC2-related disorders.
Substances chimiques
DNA
9007-49-2
Xeroderma Pigmentosum Group D Protein
EC 3.6.4.12
ERCC2 protein, human
EC 5.99.-
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
842-848Informations de copyright
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
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