DNA methylation episignature in Gabriele-de Vries syndrome
Florian Cherik
(1)
,
Jack Reilly
(2)
,
Jennifer Kerkhof
(3)
,
Michael Levy
(3)
,
Haley Mcconkey
(3)
,
Mouna Barat-Houari
(4)
,
Kameryn M Butler
(5)
,
Christine Coubes
(4)
,
Jennifer A Lee
(5)
,
Gwenael Le Guyader
(6)
,
Raymond J Louie
(5)
,
Wesley G Patterson
(5)
,
Matthew L Tedder
(5)
,
Mads Bak
(7)
,
Trine Bjørg Hammer
(7)
,
William Craigen
(8)
,
Florence Démurger
(9)
,
Christèle Dubourg
(10, 11)
,
Mélanie Fradin
(12)
,
Rachel Franciskovich
(8)
,
Eirik Frengen
(13)
,
Jennifer Friedman
(14)
,
Nathalie Ruiz Palares
(4)
,
Maria Iascone
(15)
,
Doriana Misceo
(13)
,
Pauline Monin
(16)
,
Sylvie Odent
(10, 12)
,
Christophe Philippe
(17)
,
Flavien Rouxel
(4)
,
Veronica Saletti
(18)
,
Petter Strømme
(13)
,
Perla Cassayre Thulin
(19)
,
Bekim Sadikovic
(2, 3)
,
David Genevieve
(4)
1
CHU Clermont-Ferrand
2 UWO - University of Western Ontario
3 LHSC - London Health Sciences Center
4 CHU Montpellier
5 The Greenwood Genetic Center
6 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
7 Rigshospitalet [Copenhagen]
8 BCM - Baylor College of Medicine
9 CHBA - Centre hospitalier Bretagne Atlantique (Morbihan)
10 IGDR - Institut de Génétique et Développement de Rennes
11 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
12 Centre de référence Maladies Rares CLAD-Ouest [Rennes]
13 Oslo University Hospital [Oslo]
14 UC San Diego - University of California [San Diego]
15 Hosp P Giovanni XXIII - Hospital Papa Giovanni XXIII
16 HFME - Hôpital Femme Mère Enfant [CHU - HCL]
17 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
18 Fondazione IRCCS Istituto Neurologico "Carlo Besta"
19 University of Utah
2 UWO - University of Western Ontario
3 LHSC - London Health Sciences Center
4 CHU Montpellier
5 The Greenwood Genetic Center
6 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
7 Rigshospitalet [Copenhagen]
8 BCM - Baylor College of Medicine
9 CHBA - Centre hospitalier Bretagne Atlantique (Morbihan)
10 IGDR - Institut de Génétique et Développement de Rennes
11 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
12 Centre de référence Maladies Rares CLAD-Ouest [Rennes]
13 Oslo University Hospital [Oslo]
14 UC San Diego - University of California [San Diego]
15 Hosp P Giovanni XXIII - Hospital Papa Giovanni XXIII
16 HFME - Hôpital Femme Mère Enfant [CHU - HCL]
17 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
18 Fondazione IRCCS Istituto Neurologico "Carlo Besta"
19 University of Utah
Jennifer Kerkhof
- Fonction : Auteur
- PersonId : 800226
- ORCID : 0000-0003-1245-6606
Michael Levy
- Fonction : Auteur
- PersonId : 766190
- ORCID : 0000-0002-7969-8346
Mélanie Fradin
- Fonction : Auteur
- PersonId : 770262
- ORCID : 0000-0002-2535-2198
Christophe Philippe
- Fonction : Auteur
- PersonId : 761163
- IdRef : 083945237
Bekim Sadikovic
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- Fonction : Auteur correspondant
- PersonId : 1103091
Connectez-vous pour contacter l'auteur
David Genevieve
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- Fonction : Auteur correspondant
- PersonId : 907874
- ORCID : 0000-0001-6928-6287
- IdRef : 068913532
Connectez-vous pour contacter l'auteur
Résumé
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.