2026-05-08T22:19:16Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/199152024-09-27T08:05:04Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Gonzalez-Gomez, Cristina author Del Campo Cano, Iván author Isabel Fernández-Avila, Ana author Paz Suárez-Mier, Maria author José Sagastizábal, María author Álvarez García-Rovés, Reyes author Méndez Fernández, Irene author Vilches, Silvia author Centeno Jiménez, Miriam author Siles Sánchez-Manjavacas, Ana author Usano Carrasco, Ana author Gonzalez-Vioque, Emiliano author Pablo Ochoa, Juan author Medrano, Constancio author González López, Esther author Garcia-Pavia, Pablo author Bermejo, Javier author Angeles Espinosa Castro, María author 2024-07-20 Biallelic variants in PPA2 gene cause a rare but lethal mitochondrial disorder. We describe the first four cases reported in Spain of PPA2 disease in two unrelated families. We have conducted a revision of the clinical history, necropsies, and postmortem genetic testing from probands, and clinical evaluation, genetic testing and blood transcript analysis in family members. All the cases harbored biallelic PPA2 variants in compound heterozygous status. Two brothers from family 1 suffered sudden death after a small first intake of alcohol in 2013 and 2022. The sister remains alive but affected with cardiomyopathy, extensive scar on cardiac imaging, and high sensitivity to alcohol intake. The three siblings carried PPA2 c.290A > G (p.Glu97Gly) novel missense variant and PPA2 c.513C > T (p.Cys171 = ) altering splicing site variant, both probably leading to mRNA degradation based on in-silico and transcript analyses. A teenager from family 2 suffered sudden death after a small intake of alcohol in 2018 and carried PPA2 c.683C > T (p.Pro228Leu) missense and PPA2 c.980_983del (p.Gln327fs) novel frameshift variant, both probably leading to abnormal protein structure. All cases were asymptomatic until adolescence. Furthermore, the sister in family 1 has survived as an asymptomatic adult. PPA2 disease can manifest as cardiac arrest in the young, especially after alcohol exposure. Our results show that PPA2 deficiency can be related to different pathogenicity mechanisms such as abnormal protein structure but also mRNA decay caused by synonymous or missense variants. Strict avoidance of alcohol consumption and early defibrillator implantation might prevent lethal arrhythmias in patients at risk. Gene. 2024 Jul 20:916:148437. 10.1016/j.gene.2024.148437 1879-0038 Gene 38582264 http://hdl.handle.net/20.500.12105/19915 Sudden cardiac death triggered by minimal alcohol consumption in the context of novel PPA2 mutations in 2 unrelated families.