Identification of a Novel 15q21.1 Microdeletion in a Family with Marfan Syndrome
Rencong Yang1, Wu Zhang2, Hua Lu1
1Department of Cardiovascular Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, China.
Background:
Marfan syndrome (MFS) is a connective tissue disease involving multiple systems, with thoracic aortic aneurysm (TAA) as the most common life-threatening manifestation.
Method:
A pedigree with TAA was investigated, and peripheral venous blood was extracted from six family members. After whole exome sequencing (WES) and chromosomal microarray analysis (CMA) in these individuals, bioinformatics and inheritance analyses were performed.
Result:
WES revealed a novel, small, 0.76 Mb microdeletion in 15q21.1, which cosegregated with the disease phenotype in the family and led to the haploinsufficiency of the fibrillin 1 (FBN1) gene, which is associated with MFS. This small copy number variant (CNV) was confirmed by CMA.
Conclusion:
Our study expands the phenotypic spectrum of the pathogenic CNV associated with MFS, thereby facilitating clinical genetic diagnosis and future genetic counseling for this family.
Insights
A novel microdeletion in FBN1 gene causes Marfan syndrome (MFS) with thoracic aortic aneurysm (TAA). This genetic finding aids diagnosis and counseling for affected families.
Area of Science:
- Genetics
- Molecular Biology
- Medical Science
Background:
- Marfan syndrome (MFS) is a systemic connective tissue disorder.
- Thoracic aortic aneurysm (TAA) is the most frequent life-threatening complication of MFS.
Purpose of the Study:
- To identify the genetic cause of Marfan syndrome (MFS) in a family with thoracic aortic aneurysm (TAA).
- To characterize a novel genetic variant associated with MFS.
Main Methods:
- Whole exome sequencing (WES) and chromosomal microarray analysis (CMA) were performed on family members.
- Bioinformatics and inheritance analyses were conducted to identify causative genetic variants.
Main Results:
- A novel 0.76 Mb microdeletion in 15q21.1 was identified, co-segregating with TAA in the family.
- This microdeletion results in haploinsufficiency of the fibrillin 1 (FBN1) gene, a known MFS-associated gene.
- The copy number variant (CNV) was confirmed by CMA.
Conclusions:
- The identified pathogenic CNV expands the known spectrum of genetic causes for MFS.
- This finding facilitates genetic diagnosis and counseling for families affected by MFS and TAA.
More Related Videos
08:22A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene
Published on: September 16, 2019
05:51A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011