Phenotypes and genotypes in non-consanguineous and consanguineous primary microcephaly: High incidence of epilepsy.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Duerinckx Sarah, Désir Julie, Perazzolo Camille, Badoer Cindy, Jacquemin Valérie, Soblet Julie, Maystadt Isabelle, Tunca Yusuf, Blaumeiser Bettina, Ceulemans Berten, Courtens Winnie, Debray François-Guillaume, Destree Anne, Devriendt Koenraad, Jansen Anna, Keymolen Kathelijn, Lederer Damien, Loeys Bart, Meuwissen Marije, Moortgat Stéphanie, Mortier Geert, Nassogne Marie-Cécile, Sekhara Tayeb, Van Coster Rudy, Van Den Ende Jenny, Van der Aa Nathalie, Van Esch Hilde, Vanakker Olivier, Verhelst Helene, Vilain Catheline, Weckhuysen Sarah, Passemard Sandrine, Verloes Alain, Aeby Alec, Deconinck Nicolas, Van Bogaert Patrick, Pirson Isabelle, Abramowicz Marc
Аннотация
METHODS: We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients.
RESULTS: Pathogenic variants in ASPM and WDR62 were the most frequent causes in non-consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non-consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types.
CONCLUSION: Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients.