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A recurrent, non-penetrant sequence variant, p.Arg266Cys in Growth/Differentiation Factor 3 (GDF3) in a female with unilateral anophthalmia and skeletal anomalies
PURPOSE: The genetic causes of anophthalmia, microphthalmia and coloboma remain poorly understood. Missense mutations in Growth/Differentiation Factor 3 (GDF3) gene have previously been reported in patients with microphthalmia, iridial and retinal colobomas, Klippel-Feil anomaly with vertebral fusio...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722175/ https://www.ncbi.nlm.nih.gov/pubmed/29260090 http://dx.doi.org/10.1016/j.ajoc.2017.06.006 |
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author | Bardakjian, Tanya Krall, Max Wu, Di Lao, Richard Tang, Paul Ling-Fung Wan, Eunice Kopinsky, Sarina Schneider, Adele Kwok, Pui-yan Slavotinek, Anne |
author_facet | Bardakjian, Tanya Krall, Max Wu, Di Lao, Richard Tang, Paul Ling-Fung Wan, Eunice Kopinsky, Sarina Schneider, Adele Kwok, Pui-yan Slavotinek, Anne |
author_sort | Bardakjian, Tanya |
collection | PubMed |
description | PURPOSE: The genetic causes of anophthalmia, microphthalmia and coloboma remain poorly understood. Missense mutations in Growth/Differentiation Factor 3 (GDF3) gene have previously been reported in patients with microphthalmia, iridial and retinal colobomas, Klippel-Feil anomaly with vertebral fusion, scoliosis, rudimentary 12th ribs and an anomalous right temporal bone. We used whole exome sequencing with a trio approach to study a female with unilateral anophthalmia, kyphoscoliosis and additional skeletal anomalies. OBSERVATIONS: Exome sequencing revealed that the proposita was heterozygous for c.796C > T, predicting p.Arg266Cys, in GDF3. Sanger sequencing confirmed the mutation and showed that the unaffected mother was heterozygous for the same missense substitution. CONCLUSIONS AND IMPORTANCE: Although transfection studies with the p.Arg266Cys mutation have shown that this amino acid substitution is likely to impair function, non-penetrance for the ocular defects was apparent in this family and has been observed in other families with sequence variants in GDF3. We conclude p.Arg266Cys and other GDF3 mutations can be non-penetrant, making pathogenicity more difficult to establish when sequence variants in this gene are present in patients with structural eye defects. |
format | Online Article Text |
id | pubmed-5722175 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-57221752017-12-19 A recurrent, non-penetrant sequence variant, p.Arg266Cys in Growth/Differentiation Factor 3 (GDF3) in a female with unilateral anophthalmia and skeletal anomalies Bardakjian, Tanya Krall, Max Wu, Di Lao, Richard Tang, Paul Ling-Fung Wan, Eunice Kopinsky, Sarina Schneider, Adele Kwok, Pui-yan Slavotinek, Anne Am J Ophthalmol Case Rep Case report PURPOSE: The genetic causes of anophthalmia, microphthalmia and coloboma remain poorly understood. Missense mutations in Growth/Differentiation Factor 3 (GDF3) gene have previously been reported in patients with microphthalmia, iridial and retinal colobomas, Klippel-Feil anomaly with vertebral fusion, scoliosis, rudimentary 12th ribs and an anomalous right temporal bone. We used whole exome sequencing with a trio approach to study a female with unilateral anophthalmia, kyphoscoliosis and additional skeletal anomalies. OBSERVATIONS: Exome sequencing revealed that the proposita was heterozygous for c.796C > T, predicting p.Arg266Cys, in GDF3. Sanger sequencing confirmed the mutation and showed that the unaffected mother was heterozygous for the same missense substitution. CONCLUSIONS AND IMPORTANCE: Although transfection studies with the p.Arg266Cys mutation have shown that this amino acid substitution is likely to impair function, non-penetrance for the ocular defects was apparent in this family and has been observed in other families with sequence variants in GDF3. We conclude p.Arg266Cys and other GDF3 mutations can be non-penetrant, making pathogenicity more difficult to establish when sequence variants in this gene are present in patients with structural eye defects. Elsevier 2017-06-21 /pmc/articles/PMC5722175/ /pubmed/29260090 http://dx.doi.org/10.1016/j.ajoc.2017.06.006 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Case report Bardakjian, Tanya Krall, Max Wu, Di Lao, Richard Tang, Paul Ling-Fung Wan, Eunice Kopinsky, Sarina Schneider, Adele Kwok, Pui-yan Slavotinek, Anne A recurrent, non-penetrant sequence variant, p.Arg266Cys in Growth/Differentiation Factor 3 (GDF3) in a female with unilateral anophthalmia and skeletal anomalies |
title | A recurrent, non-penetrant sequence variant, p.Arg266Cys in Growth/Differentiation Factor 3 (GDF3) in a female with unilateral anophthalmia and skeletal anomalies |
title_full | A recurrent, non-penetrant sequence variant, p.Arg266Cys in Growth/Differentiation Factor 3 (GDF3) in a female with unilateral anophthalmia and skeletal anomalies |
title_fullStr | A recurrent, non-penetrant sequence variant, p.Arg266Cys in Growth/Differentiation Factor 3 (GDF3) in a female with unilateral anophthalmia and skeletal anomalies |
title_full_unstemmed | A recurrent, non-penetrant sequence variant, p.Arg266Cys in Growth/Differentiation Factor 3 (GDF3) in a female with unilateral anophthalmia and skeletal anomalies |
title_short | A recurrent, non-penetrant sequence variant, p.Arg266Cys in Growth/Differentiation Factor 3 (GDF3) in a female with unilateral anophthalmia and skeletal anomalies |
title_sort | recurrent, non-penetrant sequence variant, p.arg266cys in growth/differentiation factor 3 (gdf3) in a female with unilateral anophthalmia and skeletal anomalies |
topic | Case report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722175/ https://www.ncbi.nlm.nih.gov/pubmed/29260090 http://dx.doi.org/10.1016/j.ajoc.2017.06.006 |
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