Molecular and Clinical Insights into KMT2E-Related O'Donnell-Luria-Rodan Syndrome in a Novel Patient Cohort.

Autor: Vecchio D; Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy. Electronic address: davide.vecchio@opbg.net., Panfili FM; Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy., Macchiaiolo M; Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy., Dentici ML; Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy., Trivisano M; Epilepsy and Movement Disorders Unit, Bambino Gesù Children's Hospital, IRCCS, Full Member of European Reference Network EpiCARE, Rome, Italy., Benitez Medina C; Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy., Capolino R; Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy., Salzano E; Medical Genetics Unit, Department of Genetics, Oncohaematology and Rare Diseases, AOOR Villa Sofia-Cervello, Palermo, Italy., Cortellessa F; Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy., Busè M; Medical Genetics Unit, Department of Genetics, Oncohaematology and Rare Diseases, AOOR Villa Sofia-Cervello, Palermo, Italy., Pantaleo A; Medical Genetics Unit, Department of Genetics, Oncohaematology and Rare Diseases, AOOR Villa Sofia-Cervello, Palermo, Italy., Cocciadiferro D; Translational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Gonfiantini MV; Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy., Niceta M; Molecular Genetics and Functional Genomics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., De Dominicis A; Epilepsy and Movement Disorders Unit, Bambino Gesù Children's Hospital, IRCCS, Full Member of European Reference Network EpiCARE, Rome, Italy., Specchio N; Epilepsy and Movement Disorders Unit, Bambino Gesù Children's Hospital, IRCCS, Full Member of European Reference Network EpiCARE, Rome, Italy., Piccione M; Medical Genetics Unit, Department of Genetics, Oncohaematology and Rare Diseases, AOOR Villa Sofia-Cervello, Palermo, Italy; Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy., Digilio MC; Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy., Tartaglia M; Molecular Genetics and Functional Genomics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Novelli A; Translational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Bartuli A; Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy.
Jazyk: angličtina
Zdroj: European journal of medical genetics [Eur J Med Genet] 2024 Dec 19, pp. 104990. Date of Electronic Publication: 2024 Dec 19.
DOI: 10.1016/j.ejmg.2024.104990
Abstrakt: 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.
(Copyright © 2024. Published by Elsevier Masson SAS.)
Databáze: MEDLINE
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