O'Donnell-Luria-Rodan syndrome
| Autor: | Camille Kumps, Heather Paterson, Benoît Funalot, Marjon van Slegtenhorst, Ingrid M.B.H. van de Laar, Robin Clark, Elliott H. Sherr, Marion Gérard, Jasmine L.F. Fung, Emanuela Argilli, Megan E. Rech, Antonio Vitobello, Christian Netzer, Christian P. Schaaf, Coranne D. Aarts-Tesselaar, Angela Abicht, Lennart Lessmeier, Brian H.Y. Chung, Anne-Sophie Denommé-Pichon, Jason Carmichael, Frédéric Tran Mau-Them, Andrea Superti-Furga, Marion Aubert Mucca, Marcus Cy Chan, Nicolas Chassaing, Christine Coubes, Anne H. O’Donnell-Luria, Lynn Pais, Colleen Kennedy, Daphné Lehalle, Maries Joseph, Kathleen A. Leppig, Florian Erger, John Karl de Dios, Lance H. Rodan, Marjolaine Willems, Subhadra Ramanathan, Clara Velmans, Eleina M. England |
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| Přispěvatelé: | Clinical Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
0301 basic medicine
Pediatrics Autism Spectrum Disorder behavioural Autism Medical and Health Sciences 0302 clinical medicine Neurodevelopmental disorder Intellectual disability 2.1 Biological and endogenous factors Aetiology Child Exome Genetics (clinical) Pediatric Genetics & Heredity Syndrome Biological Sciences Mental Health Autism spectrum disorder Cohort medicine.symptom medicine.medical_specialty Genetic counseling Intellectual and Developmental Disabilities (IDD) human genetics Article 03 medical and health sciences Seizures Clinical Research Intellectual Disability Exome Sequencing medicine Genetics Humans business.industry Human Genome Macrocephaly Neurosciences medicine.disease Human genetics Megalencephaly Brain Disorders 030104 developmental biology Neurodevelopmental Disorders Congenital Structural Anomalies mutation business 030217 neurology & neurosurgery genetic counselling |
| Zdroj: | Journal of Medical Genetics, 59(7), 697-705. BMJ Publishing Group Journal of medical genetics, vol 59, iss 7 J Med Genet |
| ISSN: | 1468-6244 0022-2593 |
| Popis: | BackgroundO’Donnell-Luria-Rodan syndrome (ODLURO) is an autosomal-dominant neurodevelopmental disorder caused by pathogenic, mostly truncating variants in KMT2E. It was first described by O’Donnell-Luria et al in 2019 in a cohort of 38 patients. Clinical features encompass macrocephaly, mild intellectual disability (ID), autism spectrum disorder (ASD) susceptibility and seizure susceptibility.MethodsAffected individuals were ascertained at paediatric and genetic centres in various countries by diagnostic chromosome microarray or exome/genome sequencing. Patients were collected into a case cohort and were systematically phenotyped where possible.ResultsWe report 18 additional patients from 17 families with genetically confirmed ODLURO. We identified 15 different heterozygous likely pathogenic or pathogenic sequence variants (14 novel) and two partial microdeletions of KMT2E. We confirm and refine the phenotypic spectrum of the KMT2E-related neurodevelopmental disorder, especially concerning cognitive development, with rather mild ID and macrocephaly with subtle facial features in most patients. We observe a high prevalence of ASD in our cohort (41%), while seizures are present in only two patients. We extend the phenotypic spectrum by sleep disturbances.ConclusionOur study, bringing the total of known patients with ODLURO to more than 60 within 2 years of the first publication, suggests an unexpectedly high relative frequency of this syndrome worldwide. It seems likely that ODLURO, although just recently described, is among the more common single-gene aetiologies of neurodevelopmental delay and ASD. We present the second systematic case series of patients with ODLURO, further refining the mutational and phenotypic spectrum of this not-so-rare syndrome. |
| Databáze: | OpenAIRE |
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