Biallelic variants in genes previously associated with dominant inheritance: CACNA1A, RET and SLC20A2

Autor: Maria Isabel Alvarez-Mora, C Palma Milla, Juan Francisco Quesada-Espinosa, Ana Arteche-López, I Gomez Manjón, I Hidalgo Mayoral, M T Sánchez Calvin, J M Lezana Rosales, Miguel A. Martín, M. Moreno-García, L I González Granado, A Juarez Rufián, R Pérez de la Fuente, O Sierra Tomillo, I J Posada Rodríguez, P Ramos Gómez, Alberto Blázquez, M J Gómez Rodríguez
Rok vydání: 2020
Předmět:
Zdroj: European Journal of Human Genetics
Eur J Hum Genet
ISSN: 1476-5438
Popis: A subset of families with co-dominant or recessive inheritance has been described in several genes previously associated with dominant inheritance. Those recessive families displayed similar, more severe, or even completely different phenotypes to their dominant counterparts. We report the first patients harboring homozygous disease-related variants in three genes that were previously associated with dominant inheritance: a loss-of-function variant in the CACNA1A gene and two missense variants in the RET and SLC20A2 genes, respectively. All patients presented with a more severe clinical phenotype than the corresponding typical dominant form. We suggest that co-dominant or recessive inheritance for these three genes could explain the phenotypic differences from those documented in their cognate dominant phenotypes. Our results reinforce that geneticists should be aware of the possible different forms of inheritance in genes when WES variant interpretation is performed. We also evidence the need to refine phenotypes and inheritance patterns associated with genes in order to avoid failures during WES analysis and thus, raising the WES diagnostic capacity in the benefit of patients.
Databáze: OpenAIRE
Externí odkaz: