RT Journal Article
SR Electronic
T1 Newly designed 11-gene panel reveals first case of hereditary amyloidosis captured by massive parallel sequencing
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 687
OP 694
DO 10.1136/jclinpath-2017-204978
VO 71
IS 8
A1 Zuzana Chyra Kufova
A1 Tereza Sevcikova
A1 Jaroslav Januska
A1 Petr Vojta
A1 Arpad Boday
A1 Pavla Vanickova
A1 Jana Filipova
A1 Katerina Growkova
A1 Tomas Jelinek
A1 Marian Hajduch
A1 Roman Hajek
YR 2018
UL http://jcp.bmj.com/content/71/8/687.abstract
AB 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.