Identifying pathogenic variants in the Follistatin‐like 1 gene (FSTL1) in patients with skeletal and atrioventricular valve disorders. Issue 4 (5th February 2019)

• Record Type: Journal Article
• Authors: Prakash, Stuti; Mattiotti, Andrea; Sylva, Marc; Mulder, Barbara J. M.; Postma, Alex V.; van den Hoff, Maurice J. B.
• Is Part Of: Molecular genetics & genomic medicine. Volume 7:Issue 4(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-02-05
• Subjects: Fstl1 -- gene expression -- heart development -- skeletal abnormalities; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.567
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: Follistatin‐like 1 (Fstl1) is a glycoprotein expressed throughout embryonic development. Homozygous loss of Fstl1 in mice results in skeletal and respiratory defects, leading to neonatal death due to a collapse of the trachea. Furthermore, Fstl1 conditional deletion from the endocardial/endothelial lineage results in postnatal death due to heart failure and profound atrioventricular valve defects. Here, we investigated patients with phenotypes similar to the phenotypes observed in the transgenic mice, for variants in FSTL1 . Methods: In total, 69 genetically unresolved patients were selected with the following phenotypes: campomelic dysplasia (12), small patella syndrome (2), BILU (1), and congenital heart disease patients (54), of which 16 also had kyphoscoliosis, and 38 had valve abnormalities as their main diagnosis. Using qPCR, none of 69 patients showed copy number variations in FSTL1 . The entire gene body, including microRNA‐198 and three validated microRNA‐binding sites, were analyzed using Sanger sequencing. Results: No variants were found in the coding region. However, 8 intronic variants were identified that differed significantly in their minor allele frequency compared to controls. Variant rs2272515 was found to significantly correlate ( p < 0.05) with kyphoscoliosis. Conclusion: We conclude that pathogenic variants in FSTL1 are unlikely to be responsible for skeletal or atrioventricular valve anomalies in humans. Abstract : In total 69 genetically unresolved patients were selected with the following phenotypes: campomelic dysplasia (12), small patella syndrome (2), BILU (1) and congenital heart disease patients (54), were screened for copy number variation and mutations in the secreted glycoprotein Follistatin‐like 1. No variants were found in the coding region. Eight intronic variants were identified that differed significantly in their minor allele frequency compared to controls, of which variant rs2272515 correlated significantly ( p < 0.05) with kyphoscoliosis.