Hemi- and homozygous loss-of-function mutations in DSG2 (Desmoglein-2) cause recessive arrhythmogenic cardiomyopathy with an early onset

Brodehl, A.; Meshkov, A.; Myasnikov, R.; Kiseleva, A.; Kulikova, O.; Klauke, B.; Sotnikova, E.; Stanasiuk, C.; Divashuk, M.; Pohl, G.M.; Kudryavtseva, M.; Klingel, K.; Gerull, B.; Zharikova, A.; Gummert, J.; Koretskiy, S.; Schubert, S.; Mershina, E.; Gärtner, A.; Pilus, P.; Laser, K.T.; Sinitsyn, V.; Boytsov, S.; Drapkina, O.; Milting, H.

Авторы: Brodehl Andreas, Meshkov Alexey, Myasnikov Roman, Kiseleva Anna, Kulikova Olga, Klauke Bärbel, Sotnikova Evgeniia, Stanasiuk Caroline, Divashuk Mikhail, Pohl Greta Marie, Kudryavtseva Maria, Klingel Karin, Gerull Brenda, Zharikova Anastasia, Gummert Jan, Koretskiy Sergey, Schubert Stephan, Mershina Elena, Gärtner Anna, Pilus Polina, Laser Kai Thorsten, Sinitsyn Valentin, Boytsov Sergey, Drapkina Oxana, Milting Hendrik
Журнал: International Journal of Molecular Sciences
Том: 22
Номер: 7
Год издания: 2021
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Первая страница: 1
Последняя страница: 15
Номер статьи: 3786
DOI: 10.3390/ijms22073786
Аннотация: 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.
Добавил в систему: Мершина Елена Александровна

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Hemi- and homozygous loss-of-function mutations in DSG2 (Desmoglein-2) cause recessive arrhythmogenic cardiomyopathy with an early onsetстатья Электронная публикация

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