Molecular and clinical Insights into KMT2E-Related O'Donnell-Luria-Rodan syndrome in a novel patient cohort
O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant neurodevelopmental disorder mainly characterized by global development delay/intellectual disability, white matter abnormalities, and behavioral manifestations. It is caused by pathogenic variants in the KMT2E gene. Here we report seven new patients with loss-of-function KMT2E variants, six harboring frameshift/nonsense changes, and one with a 7q22.3 microdeletion encompassing the entire gene-locus. We further characterize both the clinical phenotype as well as its associated pathogenic variants' spectrum providing new information on sex-related phenotype distribution, according to the variant groups. We also highlight different epilepsy phenotype-genotype correlation with preferential association of generalized epilepsy and/or developmental and epileptic encephalopathy with missense pathogenic variants and focal epilepsy, childhood absence epilepsy and/or febrile seizures with pathogenic truncating variants and structural rearrangements. By a systematic review of the previously reported series, we also discuss previously unappreciated findings, including progressive macrocephaly, apraxia, and higher risk of bone fractures.
Authors
- Marcello Niceta (ORCID: https://orcid.org/0000-0003-4766-7753)
- M. Cristina Digilio (ORCID: https://orcid.org/0000-0002-9168-3606)
- C. Medina (ORCID: https://orcid.org/0000-0002-8664-2666)
- Filippo Maria Panfili (ORCID: https://orcid.org/0000-0002-0610-325X)
- Maria Lisa Dentici (ORCID: https://orcid.org/0000-0002-9505-5906)
- Michaela Veronika Gonfiantini
- Andrea Bartuli (ORCID: https://orcid.org/0000-0001-9765-7460)
- Rossella Capolino
- Emanuela Salzano (ORCID: https://orcid.org/0000-0002-5003-1396)
- Marina Trivisano (ORCID: https://orcid.org/0000-0002-9841-8581)
- Angela De Dominicis (ORCID: https://orcid.org/0000-0002-8526-1511)
- Fabiana Cortellessa
- Antonio Pantaleo
- Martina Busè (ORCID: https://orcid.org/0000-0003-0825-9159)
- Nicola Specchio (ORCID: https://orcid.org/0000-0002-8120-0287)
- Marina Macchiaiolo (ORCID: https://orcid.org/0000-0001-7409-8299)
- Davide Vecchio (ORCID: https://orcid.org/0000-0003-2907-3206)
- Maria Piccione (ORCID: https://orcid.org/0000-0001-6053-7000)
- Dario Cocciadiferro (ORCID: https://orcid.org/0000-0002-8583-3866)
- Antonio Novelli
- Marco Tartaglia
Institutions
- Ospedale Vincenzo Cervello (IT)
- Bambino Gesù Children's Hospital (IT)
- University of Palermo (IT)
Publication Details
- Journal
- European Journal of Medical Genetics
- Published
- 2024-12-20
- DOI
- https://doi.org/10.1016/j.ejmg.2024.104990
- Citations
- 3
- Primary Topic
- Metabolism and Genetic Disorders
- Type
- article
- Field-Weighted Citation Impact
- 1.14
Funders
- Ministero della Salute