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- Publisher Website: 10.1136/jmedgenet-2020-107470
- Scopus: eid_2-s2.0-85111631770
- PMID: 34321323
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Article: O'Donnell-Luria-Rodan syndrome: description of a second multinational cohort and refinement of the phenotypic spectrum
Title | O'Donnell-Luria-Rodan syndrome: description of a second multinational cohort and refinement of the phenotypic spectrum |
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Authors | Velmans, ClaraO'Donnell-Luria, Anne H.Argilli, EmanuelaTran Mau-Them, FredericVitobello, AntonioChan, Marcus C.Y.Fung, Jasmine Lee FongRech, MeganAbicht, AngelaAubert Mucca, MarionCarmichael, JasonChassaing, NicolasClark, RobinCoubes, ChristineDenommé-Pichon, Anne SophieDe Dios, John KarlEngland, EleinaFunalot, BenoitGerard, MarionJoseph, MariesKennedy, ColleenKumps, CamilleWillems, MarjolaineVan De Laar, Ingrid M.B.H.Aarts-Tesselaar, CoranneVan Slegtenhorst, MarjonLehalle, DaphnéLeppig, KathleenLessmeier, LennartPais, Lynn S.Paterson, HeatherRamanathan, SubhadraRodan, Lance H.Superti-Furga, AndreaChung, Brian H.Y.Sherr, ElliottNetzer, ChristianSchaaf, Christian P.Erger, Florian |
Keywords | behavioural genetic counselling genetics human genetics mutation |
Issue Date | 1-Jul-2022 |
Publisher | BMJ Publishing Group |
Citation | Journal of Medical Genetics, 2022, v. 59, n. 7, p. 697-705 How to Cite? |
Abstract | Background O'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. Methods Affected 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. Results We 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. Conclusion Our 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. |
Persistent Identifier | http://hdl.handle.net/10722/348834 |
ISSN | 2023 Impact Factor: 3.5 2023 SCImago Journal Rankings: 1.690 |
DC Field | Value | Language |
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dc.contributor.author | Velmans, Clara | - |
dc.contributor.author | O'Donnell-Luria, Anne H. | - |
dc.contributor.author | Argilli, Emanuela | - |
dc.contributor.author | Tran Mau-Them, Frederic | - |
dc.contributor.author | Vitobello, Antonio | - |
dc.contributor.author | Chan, Marcus C.Y. | - |
dc.contributor.author | Fung, Jasmine Lee Fong | - |
dc.contributor.author | Rech, Megan | - |
dc.contributor.author | Abicht, Angela | - |
dc.contributor.author | Aubert Mucca, Marion | - |
dc.contributor.author | Carmichael, Jason | - |
dc.contributor.author | Chassaing, Nicolas | - |
dc.contributor.author | Clark, Robin | - |
dc.contributor.author | Coubes, Christine | - |
dc.contributor.author | Denommé-Pichon, Anne Sophie | - |
dc.contributor.author | De Dios, John Karl | - |
dc.contributor.author | England, Eleina | - |
dc.contributor.author | Funalot, Benoit | - |
dc.contributor.author | Gerard, Marion | - |
dc.contributor.author | Joseph, Maries | - |
dc.contributor.author | Kennedy, Colleen | - |
dc.contributor.author | Kumps, Camille | - |
dc.contributor.author | Willems, Marjolaine | - |
dc.contributor.author | Van De Laar, Ingrid M.B.H. | - |
dc.contributor.author | Aarts-Tesselaar, Coranne | - |
dc.contributor.author | Van Slegtenhorst, Marjon | - |
dc.contributor.author | Lehalle, Daphné | - |
dc.contributor.author | Leppig, Kathleen | - |
dc.contributor.author | Lessmeier, Lennart | - |
dc.contributor.author | Pais, Lynn S. | - |
dc.contributor.author | Paterson, Heather | - |
dc.contributor.author | Ramanathan, Subhadra | - |
dc.contributor.author | Rodan, Lance H. | - |
dc.contributor.author | Superti-Furga, Andrea | - |
dc.contributor.author | Chung, Brian H.Y. | - |
dc.contributor.author | Sherr, Elliott | - |
dc.contributor.author | Netzer, Christian | - |
dc.contributor.author | Schaaf, Christian P. | - |
dc.contributor.author | Erger, Florian | - |
dc.date.accessioned | 2024-10-17T00:30:20Z | - |
dc.date.available | 2024-10-17T00:30:20Z | - |
dc.date.issued | 2022-07-01 | - |
dc.identifier.citation | Journal of Medical Genetics, 2022, v. 59, n. 7, p. 697-705 | - |
dc.identifier.issn | 0022-2593 | - |
dc.identifier.uri | http://hdl.handle.net/10722/348834 | - |
dc.description.abstract | Background O'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. Methods Affected 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. Results We 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. Conclusion Our 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. | - |
dc.language | eng | - |
dc.publisher | BMJ Publishing Group | - |
dc.relation.ispartof | Journal of Medical Genetics | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | behavioural | - |
dc.subject | genetic counselling | - |
dc.subject | genetics | - |
dc.subject | human genetics | - |
dc.subject | mutation | - |
dc.title | O'Donnell-Luria-Rodan syndrome: description of a second multinational cohort and refinement of the phenotypic spectrum | - |
dc.type | Article | - |
dc.identifier.doi | 10.1136/jmedgenet-2020-107470 | - |
dc.identifier.pmid | 34321323 | - |
dc.identifier.scopus | eid_2-s2.0-85111631770 | - |
dc.identifier.volume | 59 | - |
dc.identifier.issue | 7 | - |
dc.identifier.spage | 697 | - |
dc.identifier.epage | 705 | - |
dc.identifier.eissn | 1468-6244 | - |
dc.identifier.issnl | 0022-2593 | - |