TY  - JOUR
A1  - Brodehl, Andreas
A1  - Meshkov, Alexey
A1  - Myasnikov, Roman
A1  - Kiseleva, Anna
A1  - Kulikova, Olga
A1  - Klauke, Bärbel
A1  - Sotnikova, Evgeniia
A1  - Stanasiuk, Caroline
A1  - Divashuk, Mikhail
A1  - Pohl, Greta Marie
A1  - Kudryavtseva, Maria
A1  - Klingel, Karin
A1  - Gerull, Brenda
A1  - Zharikova, Anastasia
A1  - Gummert, Jan
A1  - Koretskiy, Sergey
A1  - Schubert, Stephan
A1  - Mershina, Elena
A1  - Gärtner, Anna
A1  - Pilus, Polina
A1  - Laser, Kai Thorsten
A1  - Sinitsyn, Valentin
A1  - Boytsov, Sergey
A1  - Drapkina, Oxana
A1  - Milting, Hendrik
T1  - Hemi- and homozygous loss-of-function mutations in DSG2 (desmoglein-2) cause recessive arrhythmogenic cardiomyopathy with an early onset
JF  - International Journal of Molecular Sciences
N2  - About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G>T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.
KW  - desmoglein-2
KW  - desmocollin-2
KW  - DSG2
KW  - DSC2
KW  - ARVC
KW  - ACM
KW  - LVNC
KW  - cardiomyopathy
KW  - desmosomes
KW  - desmin
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285279
SN  - 1422-0067
VL  - 22
IS  - 7
ER  - 
TY  - JOUR
A1  - Gerull, Brenda
A1  - Brodehl, Andreas
T1  - Insights Into Genetics and Pathophysiology of Arrhythmogenic Cardiomyopathy
JF  - Current Heart Failure Reports
N2  - Purpose of Review
Arrhythmogenic cardiomyopathy (ACM) is a genetic disease characterized by life-threatening ventricular arrhythmias and sudden cardiac death (SCD) in apparently healthy young adults. Mutations in genes encoding for cellular junctions can be found in about half of the patients. However, disease onset and severity, risk of arrhythmias, and outcome are highly variable and drug-targeted treatment is currently unavailable.
Recent Findings
This review focuses on advances in clinical risk stratification, genetic etiology, and pathophysiological concepts. The desmosome is the central part of the disease, but other intercalated disc and associated structural proteins not only broaden the genetic spectrum but also provide novel molecular and cellular insights into the pathogenesis of ACM. Signaling pathways and the role of inflammation will be discussed and targets for novel therapeutic approaches outlined. 
Summary
Genetic discoveries and experimental-driven preclinical research contributed significantly to the understanding of ACM towards mutation- and pathway-specific personalized medicine.
KW  - dilated cardiomyopathy
KW  - arrhythmogenic cardiomyopathy
KW  - junctions
KW  - sudden cardiac death
KW  - cardiovascular genetics
KW  - desmosomes
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-269916
SN  - 1546-9549
VL  - 18
IS  - 6
ER  - 
TY  - JOUR
A1  - Brodehl, Andreas
A1  - Milting, Hendrik
A1  - Gerull, Brenda
T1  - Special Issue “Cardiovascular Genetics”
JF  - Genes
N2  - No abstract available
KW  - cardiovascular genetics
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234229
SN  - 2073-4425
VL  - 12
IS  - 4
ER  -