Fiche publication
Date publication
mars 2026
Journal
European journal of human genetics : EJHG
Auteurs
Membres identifiés du Cancéropôle Est :
Mr DUFFOURD Yannis
Tous les auteurs :
Sabbagh Q, Cenni C, Haghshenas S, Alessandri JL, Bak M, Bayat A, Barat-Houari M, Brusco A, Busa T, Calaya A, Calvert P, Cormier-Daire V, Coubes C, Duffourd Y, Ferrero GB, Guimier A, Haye D, Hjortshøj TD, Lambert L, Larsen KB, Lauzon-Young C, Lesca G, Chatron N, Levy MA, Lopergolo D, Margot H, McConkey H, Monin P, Morel G, Naudion S, Nizon M, Odent S, Pinson L, Pons L, Putoux A, Rio M, Rossi M, Rouaux L, Rouxel F, Ruiz-Pallares N, Sanchez E, Pagano S, Santorelli FM, Sauvestre C, Schymick JC, Siu VM, Spodenkiewicz M, Tedder M, Tharreau M, Mau-Them FT, Tümer Z, Valenzuela I, Van Gils J, Willems M, Kirchhoff A, Krawitz P, Kerkhof J, Schuurs-Hoeijmakers JHM, Sadikovic B, Geneviève D
Lien Pubmed
Résumé
PACS1-related disorder (PACS1-RD), also known as Schuurs-Hoeijmakers syndrome, is a rare autosomal dominant neurodevelopmental disorder predominantly caused by the recurrent de novo c.607 C > T p.(Arg203Trp) gain-of-function variant. Although core clinical features have been delineated, systematic data on developmental milestones, growth parameters, and clinical variability remain limited. We assembled a series of 24 previously unreported, unrelated individuals with PACS1-RD and compared their clinical and molecular features with 84 individuals from the literature. Genome-wide DNA methylation profiling was performed on peripheral blood DNA using bisulfite sequencing, interrogating ~860,000 CpG sites. Our study expands the phenotypic spectrum of PACS1-RD by reporting median age at independent walking and first spoken words (both 24 months), cross-sectional growth parameters, and previously undescribed clinical features, including congenital kidney malformations (25%) and feeding difficulties (75%). Compared with the literature, our series showed a higher prevalence of cryptorchidism (77.8%), congenital heart defect (45.8%), and hypotonia (75%). Methylation analysis identified a specific episignature for PACS1-RD, consistently observed in individuals carrying either the canonical p.(Arg203Trp) or the non-recurrent p.(Arg203Gln) variant. This episignature further enabled PACS1-RD diagnosis in one unsolved individual initially suspected of Kabuki syndrome. These findings refine the clinical delineation of PACS1-RD and establish an episignature that will support diagnosis in unresolved neurodevelopmental disorders and guide pathogenicity assessment of non-recurrent PACS1 variants.
Référence
Eur J Hum Genet. 2026 03 25;:
