Early-Onset Dementia Associated with a Heterozygous, Nonsense, and de novo Variant in the MBD5 Gene

Article type: Short Communication

Authors: González-Ortega, Guillermo^{a; *} | Llamas-Velasco, Sara^{a; b; c} | Arteche-López, Ana^d | Quesada-Espinosa, Juan Francisco^d | Puertas-Martín, Verónica^{a; e} | Gómez-Grande, Adolfo^f | López-Álvarez, Jorge^g | Saiz Díaz, Rosa Ana^{a; h; i} | Lezana-Rosales, José Miguel^d | Villarejo-Galende, Alberto^{a; b; c; h} | González de la Aleja, Jesús^{a; i}

Affiliations: [a] Department of Neurology, Hospital Universitario 12 de Octubre, Madrid, Spain | [b] Group of Neurodegenerative Diseases, Instituto de Investigación Hospital 12 de Octubre (I+12), Madrid, Spain | [c] Biomedical Research Networking Center in Neurodegenerative diseases CIBERNED, Madrid, Spain | [d] Department of Genetics, Hospital Universitario 12 de Octubre, Madrid, Spain | [e] Universidad Internacional de La Rioja (UNIR), Logroño, Spain | [f] Department of Nuclear Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain | [g] Department of Psychiatry, Hospital Universitario 12 de Octubre, Madrid, Spain | [h] Department of Medicine, School of Medicine, Complutense University, Madrid, Spain | [i] Epilepsy-EEG Unit, Hospital Universitario 12 de Octubre, Madrid, Spain

Correspondence: [*] Correspondence to: Dr. González-Ortega, Servicio de Neurología, Hospital Universitario 12 de Octubre, C/ Andalucía, Km 5,4. E-28041 Madrid, Spain. Tel.: +34 689077836; Fax: +34 913908600; E-mail: [email protected].

Abstract: The haploinsufficiency of the methyl-binding domain protein 5 (MBD5) gene has been identified as the determinant cause of the neuropsychiatric disorders grouped under the name MBD5-neurodevelopment disorders (MAND). MAND includes patients with intellectual disability, behavioral problems, and seizures with a static clinical course. However, a few reports have suggested regression. We describe a non-intellectually disabled female, with previous epilepsy and personality disorder, who developed early-onset dementia. The extensive etiologic study revealed a heterozygous nonsense de novo pathogenic variant in the MBD5 gene. This finding could support including the MBD5 gene in the study of patients with atypical early-onset dementia.

Keywords: Early-onset dementia, gene, human phenotype ontology, MBD5-neurodevelopment disorders, methyl-binding domain protein 5 (MBD5), personality disorder, seizures

DOI: 10.3233/JAD-210648

Journal: Journal of Alzheimer's Disease, vol. 84, no. 1, pp. 73-78, 2021