In European journal of human genetics : EJHG
Haploinsufficiency of TRIP12 causes a neurodevelopmental disorder characterized by intellectual disability associated with epilepsy, autism spectrum disorder and dysmorphic features, also named Clark-Baraitser syndrome. Only a limited number of cases have been reported to date. We aimed to further delineate the TRIP12-associated phenotype and objectify characteristic facial traits through GestaltMatcher image analysis based on deep-learning algorithms in order to establish a TRIP12 gestalt. 38 individuals between 3 and 66 years (F = 20, M = 18) - 1 previously published and 37 novel individuals - were recruited through an ERN ITHACA call for collaboration. 35 TRIP12 variants were identified, including frameshift (n = 15) and nonsense (n = 6) variants, as well as missense (n = 5) and splice (n = 3) variants, intragenic deletions (n = 4) and two multigene deletions disrupting TRIP12. Though variable in severity, global developmental delay was noted in all individuals, with language deficit most pronounced. About half showed autistic features and susceptibility to obesity seemed inherent to this disorder. A more severe expression was noted in individuals with a missense variant. Facial analysis showed a clear gestalt including deep-set eyes with narrow palpebral fissures and fullness of the upper eyelids, downturned corners of the mouth and large, often low-set ears with prominent earlobes. We report the largest cohort to date of individuals with TRIP12 variants, further delineating the associated phenotype and introducing a facial gestalt. These findings will improve future counseling and patient guidance.
Aerden Mio, Denommé-Pichon Anne-Sophie, Bonneau Dominique, Bruel Ange-Line, Delanne Julian, Gérard Bénédicte, Mazel Benoît, Philippe Christophe, Pinson Lucile, Prouteau Clément, Putoux Audrey, Tran Mau-Them Frédéric, Viora-Dupont Éléonore, Vitobello Antonio, Ziegler Alban, Piton Amélie, Isidor Bertrand, Francannet Christine, Maillard Pierre-Yves, Julia Sophie, Philippe Anais, Schaefer Elise, Koene Saskia, Ruivenkamp Claudia, Hoffer Mariette, Legius Eric, Theunis Miel, Keren Boris, Buratti Julien, Charles Perrine, Courtin Thomas, Misra-Isrie Mala, van Haelst Mieke, Waisfisz Quinten, Wieczorek Dagmar, Schmetz Ariane, Herget Theresia, Kortüm Fanny, Lisfeld Jasmin, Debray François-Guillaume, Bramswig Nuria C, Atallah Isis, Fodstad Heidi, Jouret Guillaume, Almoguera Berta, Tahsin-Swafiri Saoud, Santos-Simarro Fernando, Palomares-Bralo Maria, López-González Vanesa, Kibaek Maria, Tørring Pernille M, Renieri Alessandra, Bruno Lucia Pia, Õunap Katrin, Wojcik Monica, Hsieh Tzung-Chien, Krawitz Peter, Van Esch Hilde
2023-Feb-07
