Exome Sequencing Identifies a Novel FBN1 Variant in a Pakistani Family with Marfan Syndrome That Includes Left Ventricle Diastolic Dysfunction

• Published in: Genes 2021-11, Vol.12 (12), p.1915
• Main Authors: Farooqi, Nadia, Metherell, Louise A, Schrauwen, Isabelle, Acharya, Anushree, Khan, Qayum, Nouel Saied, Liz M, Ali, Yasir, El-Serehy, Hamed A, Jalil, Fazal, Leal, Suzanne M
• Format: Article
• Language: English
• Subjects: Adolescent; Cardiac arrhythmia; Cardiac muscle; Cardiomyopathies - complications; Cardiomyopathies - genetics; Cardiomyopathies - metabolism; Cardiomyopathies - pathology; Cardiomyopathy; Congestive heart failure; Connective tissue; Coronary artery disease; Dilated cardiomyopathy; Disease; Exome Sequencing - methods; Families & family life; Family medical history; Female; Fibrillin; Fibrillin-1 - genetics; Genes; Genetic Predisposition to Disease; Genomes; Heart failure; Humans; Male; Marfan syndrome; Marfan Syndrome - complications; Marfan Syndrome - genetics; Marfan Syndrome - metabolism; Marfan Syndrome - pathology; Middle Aged; Mutation; Pakistan; Pedigree; Phenotypes; Software; Ventricle; Ventricular Dysfunction, Left - complications; Ventricular Dysfunction, Left - genetics; Ventricular Dysfunction, Left - metabolism; Ventricular Dysfunction, Left - pathology
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12121915

Cardiomyopathies are diseases of the heart muscle and are important causes of heart failure. Dilated cardiomyopathy (DCM) is a common form of cardiomyopathy that can be acquired, syndromic or non-syndromic. The current study was conducted to explore the genetic defects in a Pakistani family with cardiac disease and features of Marfan's syndrome (MFS). A family with left ventricle (LV) diastolic dysfunction and MFS phenotype was assessed in Pakistan. The clinical information and blood samples from the patients were collected after physical, cardiovascular, and ophthalmologic examinations. An affected individual (proband) was subjected to whole-exome sequencing (WES). The findings were further validated through Sanger sequencing in the family. Through WES and sanger validation, we identified a novel variant NM_000138.4; c.1402A>G in the Fibrillin-1 ( ) gene that segregates with LV diastolic dysfunction and MFS. Furthermore, bioinformatic evaluation suggested that the novel variant is deleterious and disease-causing. This study identified for the first time a novel variant in a family with LV diastolic dysfunction and MFS in Pakistan.