OBJECTIVE: Cardiomyopathy (CMP) in children is a clinically and genetically heterogeneous group of disorders. Disease-associated mutations have been identified in more than 50 genes. Recently, mutations in the mitochondrial tRNA processing gene, ELAC2, were reported to be associated with the recessively inherited form of hypertrophic CMP (HCM). This study is aimed at describing the cardiac phenotype and outcome of ELAC2 mutation. METHODS: We performed whole exome sequencing followed by targeted mutation screening to identify the genetic etiology of severe infantile-onset CMP in 64 consanguineous Saudi families. RESULTS: A previously reported mutation (p.Phe154Leu) in ELAC2 gene was detected in 16 families. The index cases presented between 2 and 7 months of age with HCM in 13 infants and dilated CMP (DCM) in 3. Pericardial effusion was observed in 7 infants (44%). All infants died with a median age of death of 4 months. Almost 1/3 of them died during the initial presentation. CONCLUSION: Our study suggests screening the ELAC2 gene in severe infantile-onset HCM or DCM of unknown etiology, especially in the presence of pericardial effusion. Our work demonstrates a universally poor outcome of the (p.Phe154Leu) variant in ELAC2 gene; a correlation that helps in counseling parents and in planning appropriate medical intervention.
OBJECTIVE:Cardiomyopathy (CMP) in children is a clinically and genetically heterogeneous group of disorders. Disease-associated mutations have been identified in more than 50 genes. Recently, mutations in the mitochondrial tRNA processing gene, ELAC2, were reported to be associated with the recessively inherited form of hypertrophic CMP (HCM). This study is aimed at describing the cardiac phenotype and outcome of ELAC2 mutation. METHODS: We performed whole exome sequencing followed by targeted mutation screening to identify the genetic etiology of severe infantile-onset CMP in 64 consanguineous Saudi families. RESULTS: A previously reported mutation (p.Phe154Leu) in ELAC2 gene was detected in 16 families. The index cases presented between 2 and 7 months of age with HCM in 13 infants and dilated CMP (DCM) in 3. Pericardial effusion was observed in 7 infants (44%). All infants died with a median age of death of 4 months. Almost 1/3 of them died during the initial presentation. CONCLUSION: Our study suggests screening the ELAC2 gene in severe infantile-onset HCM or DCM of unknown etiology, especially in the presence of pericardial effusion. Our work demonstrates a universally poor outcome of the (p.Phe154Leu) variant in ELAC2 gene; a correlation that helps in counseling parents and in planning appropriate medical intervention.
Authors: Martin Paucar; Aleksandra Pajak; Christoph Freyer; Åsa Bergendal; Margit Döry; José Miguel Laffita-Mesa; Henrik Stranneheim; Kristina Lagerstedt-Robinson; Irina Savitcheva; Ruth H Walker; Anna Wedell; Anna Wredenberg; Per Svenningsson Journal: Neurology Date: 2018-09-14 Impact factor: 9.910
Authors: Makenzie Saoura; Christopher A Powell; Robert Kopajtich; Ahmad Alahmad; Haya H Al-Balool; Buthaina Albash; Majid Alfadhel; Charlotte L Alston; Enrico Bertini; Penelope E Bonnen; Drago Bratkovic; Rosalba Carrozzo; Maria A Donati; Michela Di Nottia; Daniele Ghezzi; Amy Goldstein; Eric Haan; Rita Horvath; Joanne Hughes; Federica Invernizzi; Eleonora Lamantea; Benjamin Lucas; Kyla-Gaye Pinnock; Maria Pujantell; Shamima Rahman; Pedro Rebelo-Guiomar; Saikat Santra; Daniela Verrigni; Robert McFarland; Holger Prokisch; Robert W Taylor; Louis Levinger; Michal Minczuk Journal: Hum Mutat Date: 2019-06-18 Impact factor: 4.700