Cargando…
Identifying pathogenic variants in the Follistatin‐like 1 gene (FSTL1) in patients with skeletal and atrioventricular valve disorders
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/...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465659/ https://www.ncbi.nlm.nih.gov/pubmed/30722102 http://dx.doi.org/10.1002/mgg3.567 |
_version_ | 1783410973724377088 |
---|---|
author | Prakash, Stuti Mattiotti, Andrea Sylva, Marc Mulder, Barbara J. M. Postma, Alex V. van den Hoff, Maurice J. B. |
author_facet | Prakash, Stuti Mattiotti, Andrea Sylva, Marc Mulder, Barbara J. M. Postma, Alex V. van den Hoff, Maurice J. B. |
author_sort | Prakash, Stuti |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6465659 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64656592019-04-23 Identifying pathogenic variants in the Follistatin‐like 1 gene (FSTL1) in patients with skeletal and atrioventricular valve disorders Prakash, Stuti Mattiotti, Andrea Sylva, Marc Mulder, Barbara J. M. Postma, Alex V. van den Hoff, Maurice J. B. Mol Genet Genomic Med Original Articles 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. John Wiley and Sons Inc. 2019-02-05 /pmc/articles/PMC6465659/ /pubmed/30722102 http://dx.doi.org/10.1002/mgg3.567 Text en © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Prakash, Stuti Mattiotti, Andrea Sylva, Marc Mulder, Barbara J. M. Postma, Alex V. van den Hoff, Maurice J. B. Identifying pathogenic variants in the Follistatin‐like 1 gene (FSTL1) in patients with skeletal and atrioventricular valve disorders |
title | Identifying pathogenic variants in the Follistatin‐like 1 gene (FSTL1) in patients with skeletal and atrioventricular valve disorders |
title_full | Identifying pathogenic variants in the Follistatin‐like 1 gene (FSTL1) in patients with skeletal and atrioventricular valve disorders |
title_fullStr | Identifying pathogenic variants in the Follistatin‐like 1 gene (FSTL1) in patients with skeletal and atrioventricular valve disorders |
title_full_unstemmed | Identifying pathogenic variants in the Follistatin‐like 1 gene (FSTL1) in patients with skeletal and atrioventricular valve disorders |
title_short | Identifying pathogenic variants in the Follistatin‐like 1 gene (FSTL1) in patients with skeletal and atrioventricular valve disorders |
title_sort | identifying pathogenic variants in the follistatin‐like 1 gene (fstl1) in patients with skeletal and atrioventricular valve disorders |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465659/ https://www.ncbi.nlm.nih.gov/pubmed/30722102 http://dx.doi.org/10.1002/mgg3.567 |
work_keys_str_mv | AT prakashstuti identifyingpathogenicvariantsinthefollistatinlike1genefstl1inpatientswithskeletalandatrioventricularvalvedisorders AT mattiottiandrea identifyingpathogenicvariantsinthefollistatinlike1genefstl1inpatientswithskeletalandatrioventricularvalvedisorders AT sylvamarc identifyingpathogenicvariantsinthefollistatinlike1genefstl1inpatientswithskeletalandatrioventricularvalvedisorders AT mulderbarbarajm identifyingpathogenicvariantsinthefollistatinlike1genefstl1inpatientswithskeletalandatrioventricularvalvedisorders AT postmaalexv identifyingpathogenicvariantsinthefollistatinlike1genefstl1inpatientswithskeletalandatrioventricularvalvedisorders AT vandenhoffmauricejb identifyingpathogenicvariantsinthefollistatinlike1genefstl1inpatientswithskeletalandatrioventricularvalvedisorders |