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  - Hartlieb, Eva
A1  - Kempf, Bettina
A1  - Partilla, Miriam
A1  - Vigh, Balázs
A1  - Spindler, Volker
A1  - Waschke, Jens
T1  - Desmoglein 2 Is Less Important than Desmoglein 3 for Keratinocyte Cohesion
JF  - PLoS ONE
N2  - Desmosomes provide intercellular adhesive strength required for integrity of epithelial and some non-epithelial tissues. Within the epidermis, the cadherin-type adhesion molecules desmoglein (Dsg) 1-4 and desmocollin (Dsc) 1-3 build the adhesive core of desmosomes. In keratinocytes, several isoforms of these proteins are co-expressed. However, the contribution of specific isoforms to overall cell cohesion is unclear. Therefore, in this study we investigated the roles of Dsg2 and Dsg3, the latter of which is known to be essential for keratinocyte adhesion based on its autoantibody-induced loss of function in the autoimmune blistering skin disease pemphigus vulgaris (PV). The pathogenic PV antibody AK23, targeting the Dsg3 adhesive domain, led to profound loss of cell cohesion in human keratinocytes as revealed by the dispase-based dissociation assays. In contrast, an antibody against Dsg2 had no effect on cell cohesion although the Dsg2 antibody was demonstrated to interfere with Dsg2 transinteraction by single molecule atomic force microscopy and was effective to reduce cell cohesion in intestinal epithelial Caco-2 cells which express Dsg2 as the only Dsg isoform. To substantiate these findings, siRNA-mediated silencing of Dsg2 or Dsg3 was performed in keratinocytes. In contrast to Dsg3-depleted cells, Dsg2 knockdown reduced cell cohesion only under conditions of increased shear. These experiments indicate that specific desmosomal cadherins contribute differently to keratinocyte cohesion and that Dsg2 compared to Dsg3 is less important in this context.
KW  - expression
KW  - inhibition
KW  - DSG2
KW  - cell adhesion
KW  - desmosomal cadherins
KW  - pemphigus vulgaris
KW  - phenotype
KW  - mice
KW  - transinteraction
KW  - reorganization
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131192
VL  - 8
IS  - 1
ER  -