Next-generation sequencing and SNP arrays identified novel hemi- and homozygous loss-of-function mutations in DSG2 in two ACM patients without familial medical history, suggesting recessive inheritance.
Case Report (n=2)
Deep genetic analysis using NGS and SNP arrays identified novel recessive loss-of-function mutations in DSG2 in ACM patients without a family history, highlighting the importance of comprehensive genetic testing.
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.
Brodehl et al. (Tue,) conducted a case report in Arrhythmogenic cardiomyopathy (ACM) (n=2). Hemi- and homozygous loss-of-function mutations in DSG2 was evaluated on Identification of genetic mutations. Next-generation sequencing and SNP arrays identified novel hemi- and homozygous loss-of-function mutations in DSG2 in two ACM patients without familial medical history, suggesting recessive inheritance.
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