FOSL2 truncating variants in the last exon cause a neurodevelopmental disorder with scalp and enamel defects.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Cospain Auriane, Rivera-Barahona Ana, Dumontet Erwan, Gener Blanca, Bailleul-Forestier Isabelle, Meyts Isabelle, Jouret Guillaume, Isidor Bertrand, Brewer Carole, Wuyts Wim, Moens Leen, Delafontaine Selket, Keung Lam Wayne Wing, Van Den Bogaert Kris, Boogaerts Anneleen, Scalais Emmanuel, Besnard Thomas, Cogne Benjamin, Guissard Christophe, Rollier Paul, Carre Wilfrid, Bouvet Regis, Tarte Karin, Gómez-Carmona Ricardo, Lapunzina Pablo, Odent Sylvie, Faoucher Marie, Dubourg Christele, Ruiz-Pérez Víctor L, Devriendt Koen, Pasquier Laurent, Pérez-Jurado Luis A
Аннотация
METHODS: Exome sequencing was used to identify genetic variants in all cases, recruited through Matchmaker exchange. Gene expression in blood was analyzed using reverse transcription polymerase chain reaction. In vitro coimmunoprecipitation and proteasome inhibition assays in transfected HEK293 cells were performed to explore protein and AP-1 complex stability.
RESULTS: We identified 11 individuals from 10 families with mostly de novo truncating FOSL2 variants sharing a strikingly similar phenotype characterized by prenatal growth retardation, localized cutis scalp aplasia with or without skull defects, neurodevelopmental delay with autism spectrum disorder, enamel hypoplasia, and congenital cataracts. Mutant FOSL2 messenger RNAs escaped nonsense-mediated messenger RNA decay. Truncated FOSL2 interacts with c-JUN, thus mutated AP-1 complexes could be formed.
CONCLUSION: Truncating variants in the last exon of FOSL2 associate a distinct clinical phenotype by altering the regulatory degradation of the AP-1 complex. These findings reveal a new role for FOSL2 in human pathology.