Early-onset Nucleotide Excision Repair disorders with neurological impairment: clues for early diagnosis and prognostic counselling.
Fiche publication
Date publication
juin 2020
Journal
Clinical genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHELLY Jamel
Tous les auteurs :
Baer S, Obringer C, Julia S, Chelly J, Capri Y, Gras D, Baujat G, Felix TM, Doray B, Del Pozo JS, Ramos LM, Burglen L, Laugel V, Calmels N
Lien Pubmed
Résumé
Nucleotide Excision Repair associated diseases comprise overlapping phenotypes and a wide range of outcomes. The early stages still remain under-investigated and underdiagnosed, even though an early recognition of the first symptoms is of utmost importance for appropriate care and genetic counselling. We systematically collected clinical and molecular data from the literature and from newly diagnosed NER patients with neurological impairment, presenting clinical symptoms before the age of 12 months, including foetal cases. 185 patients were included, 13 with specific symptoms during foetal life. Arthrogryposis, microcephaly, cataracts and skin anomalies are the most frequently reported signs in early subtypes. Non ERCC6/CSB or ERCC8/CSA genes are overrepresented compared to later onset cohorts: 19% patients of this cohort presented variants in ERCC1, ERCC2/XPD, ERCC3/XPB or ERCC5/XPG. ERCC5/XPG is even the most frequently involved gene in foetal cases (10/13 cases, (4/7 families)). In this cohort, the mutated gene, the age of onset, the type of disease, severe global developmental delay, IUGR and skin anomalies were associated with earlier death. This large survey focuses on specific symptoms that should attract the attention of clinicians towards early-onset NER diagnosis in foetal and neonatal period, without waiting for the completeness of classical criteria.
Mots clés
COFS, Cockayne syndrome, NER associated disease, XP-CS, neonatal form
Référence
Clin. Genet.. 2020 Jun 17;: