Triplication of the PCDH19 Gene as a Novel Disease Mechanism Leading to Epileptic Encephalopathy Resembling Loss-of-Function Pathogenic Variants.

Fecha de publicación: 12/10/2024 Fecha Ahead of Print: 12/10/2024

Autores de IIS La Fe

Grupos

Investigación Traslacional en Genética

Leader

Francisco Martínez Castellano

Abstract

BACKGROUND/OBJECTIVES: Developmental and epileptic encephalopathy 9 (DEE9) (MIM #300088) affects heterozygous females and males with somatic pathogenic variants, while male carriers with hemizygous PCDH19 pathogenic variants are clinically unaffected. There are hundreds of pathogenic single nucleotide variants in the PCDH19 gene reported in the literature, which lead to the loss of function of the PCDH19 protein. To date, no phenotypes associated with overexpression or copy number gains have been described in this gene. METHODS AND RESULTS: We present a female patient with a de novo triplication in the Xq21.3-q22.1 chromosomal region, which includes the PCDH19 gene, which implies an unbalanced dose gain. This patient displayed a phenotype of epileptic encephalopathy compatible with DEE9. By comparison, another male patient with a similar duplication showed mild developmental delay and autism but never developed epilepsy. CONCLUSIONS: Here, we propose the dose gain of PCDH19 as a new pathogenic mechanism that results in a phenotype similar to that found in patients with loss-of-function variants in PCDH19, when present in a heterozygous state.

Datos de la publicación

ISSN/ISSNe:: 2073-4425, 2073-4425
Tipo:: Article
Páginas:: -
DOI:: 10.3390/genes15101312
Factor de Impacto:: 1,032 SCImago ℠
Cuartil:: Q2 SCImago ℠

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Filiaciones

Gabaldón-Albero A:: Translational Research Group in Genetics, La Fe Health Research Institute, 46026 Valencia, Spain
Smeyers P:: Pediatric Neurology Section, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain
Hernández-Muela S:: Pediatric Neurology Section, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain
Roselló M:: Translational Research Group in Genetics, La Fe Health Research Institute, 46026 Valencia, Spain

Genetics Unit, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
Orellana C:: Translational Research Group in Genetics, La Fe Health Research Institute, 46026 Valencia, Spain

Genetics Unit, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
Monfort S:: Translational Research Group in Genetics, La Fe Health Research Institute, 46026 Valencia, Spain

Genetics Unit, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
Oltra S:: Translational Research Group in Genetics, La Fe Health Research Institute, 46026 Valencia, Spain

Genetics Unit, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
Martínez F:: Translational Research Group in Genetics, La Fe Health Research Institute, 46026 Valencia, Spain

Genetics Unit, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain