DNA methylation episignature in Gabriele-de Vries syndrome

Florian Cherik, Jack Reilly, Jennifer Kerkhof, Michael Levy, Haley McConkey, Mouna Barat-Houari, Kameryn M Butler, Christine Coubes, Jennifer A Lee, Gwenael Le Guyader, Raymond J Louie, Wesley G Patterson, Matthew L Tedder, Mads Bak, Trine Bjørg Hammer, William Craigen, Florence Démurger, Christèle Dubourg, Mélanie Fradin, Rachel FranciskovichEirik Frengen, Jennifer Friedman, Nathalie Ruiz Palares, Maria Iascone, Doriana Misceo, Pauline Monin, Sylvie Odent, Christophe Philippe, Flavien Rouxel, Veronica Saletti, Petter Strømme, Perla Cassayre Thulin, Bekim Sadikovic, David Genevieve

7 Citationer (Scopus)


PURPOSE: Gabriele-de Vries syndrome (GADEVS) is a rare genetic disorder characterized by developmental delay and/or intellectual disability, hypotonia, feeding difficulties, and distinct facial features. To refine the phenotype and to better understand the molecular basis of the syndrome, we analyzed clinical data and performed genome-wide DNA methylation analysis of a series of individuals carrying a YY1 variant.

METHODS: Clinical data were collected for 13 individuals not yet reported through an international call for collaboration. DNA was collected for 11 of these individuals and 2 previously reported individuals in an attempt to delineate a specific DNA methylation signature in GADEVS.

RESULTS: Phenotype in most individuals overlapped with the previously described features. We described 1 individual with atypical phenotype, heterozygous for a missense variant in a domain usually not involved in individuals with YY1 pathogenic missense variations. We also described a specific peripheral blood DNA methylation profile associated with YY1 variants.

CONCLUSION: We reported a distinct DNA methylation episignature in GADEVS. We expanded the clinical profile of GADEVS to include thin/sparse hair and cryptorchidism. We also highlighted the utility of DNA methylation episignature analysis for classification of variants of unknown clinical significance.

TidsskriftGenetics in medicine : official journal of the American College of Medical Genetics
Udgave nummer4
Sider (fra-til)905-914
Antal sider10
StatusUdgivet - apr. 2022


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