Phenotypes and genotypes in non‐consanguineous and consanguineous primary microcephaly: High incidence of epilepsy
| Autor: | Bettina Blaumeiser, Alec Aeby, Marc Abramowicz, Isabelle Pirson, Cindy Badoer, Helene Verhelst, Kathelijn Keymolen, Berten Ceulemans, Hilde Van Esch, Stéphanie Moortgat, Anne Destree, Patrick Van Bogaert, Sarah Duerinckx, Yusuf Tunca, Valérie Jacquemin, Olivier Vanakker, Nicolas Deconinck, Sarah Weckhuysen, Camille Perazzolo, Marije E.C. Meuwissen, Anna Jansen, Sandrine Passemard, Damien Lederer, Winnie Courtens, Rudy Van Coster, Koenraad Devriendt, Tayeb Sekhara, Nathalie Van der Aa, Isabelle Maystadt, Bart Loeys, Julie Soblet, François-Guillaume Debray, Marie-Cécile Nassogne, Geert Mortier, Julie Désir, Alain Verloes, Catheline Vilain, Jenny Van Den Ende |
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| Přispěvatelé: | UCL - (SLuc) Service de neurologie pédiatrique, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Centre de malformations vasculaires congénitales, UCL - (SLuc) Centre de référence en lésions congénitales de la moëlle épinière, UCL - (SLuc) Centre de référence pour l'épilepsie réfractaire, Public Health Sciences, Mental Health and Wellbeing research group, Neurogenetics, Neuroprotection & Neuromodulation, Pediatrics, Clinical sciences, Medical Genetics |
| Rok vydání: | 2021 |
| Předmět: |
Male
Pediatrics Candidate gene Microcephaly ASPM MUTATIONS PROTEIN Cell Cycle Proteins QH426-470 FAMILIES Consanguinity Epilepsy Gene Frequency Medicine and Health Sciences SEQUENCE VARIANTS HETEROGENEITY Child Genetics (clinical) SNPS Genetics & Heredity Mendeliome Seizure types Incidence primary microcephaly Phenotype Cohort Original Article Female Life Sciences & Biomedicine medicine.medical_specialty Genotype rare disease Nerve Tissue Proteins ASPM Genetic Heterogeneity consanguinity Genetics medicine Humans PRENATAL-DIAGNOSIS Molecular Biology WDR62 Science & Technology Genetic heterogeneity business.industry brain developmental disorders Généralités Original Articles FRAMEWORK medicine.disease epilepsy Human medicine business |
| Zdroj: | Molecular genetics & genomic medicine MOLECULAR GENETICS & GENOMIC MEDICINE Molecular genetics & genomic medicine, Vol. 9, no. 9, p. e1768 [1-19] (2021) Molecular Genetics & Genomic Medicine Molecular Genetics & Genomic Medicine, Vol 9, Iss 9, Pp n/a-n/a (2021) |
| ISSN: | 2324-9269 |
| Popis: | Background: Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. 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. SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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