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. 2021 Nov 28;12(12):1915.
doi: 10.3390/genes12121915.

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

Nadia Farooqi  1 , Louise A Metherell  2 , Isabelle Schrauwen  3 , Anushree Acharya  3 , Qayum Khan  1 , Liz M Nouel Saied  3 , Yasir Ali  1 , Hamed A El-Serehy  4 , Fazal Jalil  1 , Suzanne M Leal  3   5
Affiliations

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

Nadia Farooqi et al. Genes (Basel). .

Abstract

Introduction: 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).

Methods: 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.

Results: Through WES and sanger validation, we identified a novel variant NM_000138.4; c.1402A>G in the Fibrillin-1 (FBN1) gene that segregates with LV diastolic dysfunction and MFS. Furthermore, bioinformatic evaluation suggested that the novel variant is deleterious and disease-causing.

Conclusions: This study identified for the first time a novel FBN1 variant in a family with LV diastolic dysfunction and MFS in Pakistan.

Keywords: Marfan syndrome; cardiovascular diseases; dilated cardiomyopathy; left ventricular diastolic dysfunction; whole exome sequencing.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Pedigree of the family. Males and females are denoted by squares and circles, respectively. Filled symbols represent affected individuals and unfilled symbols unaffected family members. Crossed symbols indicate the family member is deceased. The arrow shows the proband. The proband (II-3) in the Family underwent exome sequencing while other members in this family underwent Sanger sequencing. The genotypes are shown for the FBN1 variant [c.1402A>G: p.(T468A)].
Figure 2
Figure 2
DNA sequence chromatograms of FBN1 variant (NM_000138.4; c.1402A>G) obtained after Sanger sequencing. (a) DNA chromatogram of affected indiviudal II-3; (b) DNA chromatogram of affected indiviudal II-7; (c) DNA chromatogram of affected indiviudal III-3; (d) DNA chromatogram of unaffected indiviudal III-2.
Figure 3
Figure 3
Schematic illustration of FBN1 (Fibrillin-1), a large glycoprotein (350 kDa, 2871 amino acids) with multiple functional domains. The figure shows that the variant p.(T468A) is located in cbEGF-like domain 3 of the protein [22].
See this image and copyright information in PMC

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