TY  - JOUR
A1  - Janz, Anna
A1  - Zink, Miriam
A1  - Cirnu, Alexandra
A1  - Hartleb, Annika
A1  - Albrecht, Christina
A1  - Rost, Simone
A1  - Klopocki, Eva
A1  - Günther, Katharina
A1  - Edenhofer, Frank
A1  - Ergün, Süleyman
A1  - Gerull, Brenda
T1  - CRISPR/Cas9-edited PKP2 knock-out (JMUi001-A-2) and DSG2 knock-out (JMUi001-A-3) iPSC lines as an isogenic human model system for arrhythmogenic cardiomyopathy (ACM)
JF  - Stem Cell Research
N2  - Arrhythmogenic cardiomyopathy (ACM) is characterized by fibro-fatty replacement of the myocardium, heart failure and life-threatening ventricular arrhythmias. Causal mutations were identified in genes encoding for proteins of the desmosomes, predominantly plakophilin-2 (PKP2) and desmoglein-2 (DSG2). We generated gene-edited knock-out iPSC lines for PKP2 (JMUi001-A-2) and DSG2 (JMUi001-A-3) using the CRISPR/Cas9 system in a healthy control iPSC background (JMUi001A). Stem cell-like morphology, robust expression of pluripotency markers, embryoid body formation and normal karyotypes confirmed the generation of high quality iPSCs to provide a novel isogenic human in vitro model system mimicking ACM when differentiated into cardiomyocytes.
KW  - mutations
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259846
VL  - 53
ER  - 
TY  - JOUR
A1  - Pluta, Natalie
A1  - Hoffjan, Sabine
A1  - Zimmer, Frederic
A1  - Köhler, Cornelia
A1  - Lücke, Thomas
A1  - Mohr, Jennifer
A1  - Vorgerd, Matthias
A1  - Nguyen, Hoa Huu Phuc
A1  - Atlan, David
A1  - Wolf, Beat
A1  - Zaum, Ann-Kathrin
A1  - Rost, Simone
T1  - Homozygous inversion on chromosome 13 involving SGCG detected by short read whole genome sequencing in a patient suffering from limb-girdle muscular dystrophy
JF  - Genes
N2  - New techniques in molecular genetic diagnostics now allow for accurate diagnosis in a large proportion of patients with muscular diseases. Nevertheless, many patients remain unsolved, although the clinical history and/or the muscle biopsy give a clear indication of the involved genes. In many cases, there is a strong suspicion that the cause must lie in unexplored gene areas, such as deep-intronic or other non-coding regions. In order to find these changes, next-generation sequencing (NGS) methods are constantly evolving, making it possible to sequence entire genomes to reveal these previously uninvestigated regions. Here, we present a young woman who was strongly suspected of having a so far genetically unsolved sarcoglycanopathy based on her clinical history and muscle biopsy. Using short read whole genome sequencing (WGS), a homozygous inversion on chromosome 13 involving SGCG and LINC00621 was detected. The breakpoint in intron 2 of SGCG led to the absence of γ-sarcoglycan, resulting in the manifestation of autosomal recessive limb-girdle muscular dystrophy 5 (LGMDR5) in the young woman.
KW  - inversion
KW  - sarcoglycanopathy
KW  - whole genome sequencing (WGS)
KW  - next generation sequencing (NGS)
KW  - LGMDR5
KW  - muscle disease
KW  - genetic diagnostics
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-288122
SN  - 2073-4425
VL  - 13
IS  - 10
ER  -