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In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Frequent FBN2 variants in pectus excavatum highlight underlying phenotypic variability.
Xicheng Deng1, Yu Zheng2, Jinghua Wang1
1Department of Cardiothoracic Surgery, Central South University (Hunan Children's Hospital), Changsha, Hunan, China.
Journal of Medical Genetics
|July 6, 2026
Summary
Genetic variants in FBN2 are linked to isolated pectus excavatum (PE) in children. This study highlights the wide range of symptoms and genetic variability in FBN2-related conditions.
Area of Science:
- Genetics
- Paediatric Medicine
- Skeletal Dysplasias
Background:
- Genetic screening for radioulnar synostosis (RUS) revealed FBN2 variants in individuals with pectus excavatum (PE).
- Previous research has not fully elucidated the genetic basis of non-syndromic paediatric PE.
Purpose of the Study:
- To investigate the association between FBN2 variants and non-syndromic paediatric PE.
- To characterize the phenotypic spectrum of FBN2-related disorders.
Main Methods:
- Phenotyping of an Fbn2 knockout mouse model.
- Exome sequencing and burden analysis in 290 paediatric PE probands and controls.
- Clinical re-evaluation using the Callewaert scoring system and genotype-phenotype correlation.
- Assessment of gene expression and Bone Morphogenetic Protein (BMP) signalling in murine tissues.
Main Results:
- Fbn2-deficient mice displayed sternal abnormalities and a PE-like phenotype.
- Significant association found between rare damaging FBN2 variants and paediatric PE (OR=5.276, p<0.001).
- FBN2 variants showed broad clinical variability with minimal overlap with RUS, and reduced BMP signalling in mice.
Conclusions:
- FBN2 is identified as a significant genetic contributor to isolated paediatric PE.
- The study underscores the wide phenotypic spectrum and clinical variability of FBN2-related disorders.
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