Whole-Exome Sequencing Identified a Novel Variant (C.۴۰۵_۴۲۲+۳۹del) in DSP Gene in an Iranian Pedigree with Familial Dilated Cardiomyopathy

سال انتشار: 1400
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 521

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شناسه ملی سند علمی:

JR_RBMB-10-2_014

تاریخ نمایه سازی: 10 شهریور 1400

چکیده مقاله:

Background: Dilated cardiomyopathy (DCM) is a progressive heart condition characterized by left ventricular chamber enlargement associated with systolic heart failure and prolonged action potential duration. Genetic variations in genes that encode cytoskeleton, sarcomere, and nuclear envelope proteins are responsible for ۴۵% of cases. In our study, we focused on a pedigree with familial DCM to decipher the potential genetic cause(s) in affected members developing arrhythmia, end-stage heart failure, and sudden death. Methods: Whole-exome sequencing (WES) was exploited for a ۲۷-year-old heart-transplanted female as the proband, and the derived data were filtered using the standard pipelines. Results: A ۵۷-nucleotide deletion (c.۴۰۵_۴۲۲+۳۹del) in the desmoplakin gene (DSP) (NM_۰۰۴۴۱۵.۴) was identified as a novel pathogenic variant. Familial segregation analysis indicated that this variant is present in clinically affected members and absent in unaffected members. Conclusions: It seems that the detected variant induces intron retention, resulting in a premature stop codon in intron ۳ of DSP leading to production of a truncated, nonfunctional protein. Additionally, it can trigger a nonsense-mediated mRNA decay pathway associated with inhibition of protein production. The present study results illustrated that a novel deletion in DSP can cause DCM in an Iranian family.

نویسندگان

Yeganeh Eshaghkhani

Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Arezoo Mohamadifar

Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Science, Tehran, Iran.

Mostafa Asadollahi

Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Mahdieh Taghizadeh

Watson Genetic Laboratory, North Kargar Street, Tehran, Iran.

Arezou Karamzade

Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Mohammad Saberi

Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Parisa Nourmohammadi

Watson Genetic Laboratory, North Kargar Street, Tehran, Iran.

Zahra Golchehre

Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Ahmad Amin

Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Science, Tehran, Iran.

Mohammad Keramatipour

Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran & Watson Genetic Laboratory, North Kargar Street, Tehran, Iran.

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