AIMS: Amyloidosis is caused by deposition of abnormal protein fibrils, leading to damage of organ function. Hereditary amyloidosis represents a monogenic disease caused by germline mutations in 11 amyloidogenic precursor protein genes. One of the important but non-specific symptoms of amyloidosis is hypertrophic cardiomyopathy. Diagnostics of hereditary amyloidosis is complicated and the real cause can remain overlooked. We aimed to design hereditary amyloidosis gene panel and to introduce new next-generation sequencing (NGS) approach to investigate hereditary amyloidosis in a cohort of patients with hypertrophic cardiomyopathy of unknown significance. METHODS: Design of target enrichment DNA library preparation using Haloplex Custom Kit containing 11 amyloidogenic genes was followed by MiSeq Illumina sequencing and bioinformatics identification of germline variants using tool VarScan in a cohort of 40 patients. RESULTS: We present design of NGS panel for 11 genes (TTR, FGA, APOA1, APOA2, LYZ, GSN, CST3, PRNP, APP, B2M, ITM2B) connected to various forms of amyloidosis. We detected one mutation, which is responsible for hereditary amyloidosis. Some other single nucleotide variants are so far undescribed or rare variants or represent common polymorphisms in European population. CONCLUSIONS: We report one positive case of hereditary amyloidosis in a cohort of patients with hypertrophic cardiomyopathy of unknown significance and set up first panel for NGS in hereditary amyloidosis. This work may facilitate successful implementation of the NGS method by other researchers or clinicians and may improve the diagnostic process after validation.

Cardiocentre Podlesi Trinec Czech Republic

Department of Biology and Ecology Faculty of Science University of Ostrava Ostrava Czech Republic

Department of Clinical Studies Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic

Department of Haematooncology University Hospital Ostrava Ostrava Czech Republic

Faculty of Medicine and Dentistry Institute of Molecular and Translational Medicine Palacky University Olomouc Czech Republic

Laboratory of Molecular Biology Department of Medical Genetics Laboratory AGEL Novy Jicin Czech Republic

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