A recurrent, non-penetrant sequence variant, p.Arg266Cys in Growth/Differentiation Factor 3 ( GDF3 ) in a female with unilateral anophthalmia and skeletal anomalies
| Autor: | Paul Ling-Fung Tang, Sarina Kopinsky, Pui-Yan Kwok, Richard Lao, Max Krall, Di Wu, Anne Slavotinek, Adele Schneider, Tanya Bardakjian, Eunice Wan |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.disease_cause Microphthalmia 03 medical and health sciences symbols.namesake lcsh:Ophthalmology Case report p.Arg266Cys in GDF3 Genetics medicine 2.1 Biological and endogenous factors Missense mutation Aetiology Anophthalmia Eye Disease and Disorders of Vision Kyphoscoliosis Exome sequencing Pediatric GDF3 Sanger sequencing Mutation Coloboma business.industry Human Genome medicine.disease eye diseases Ophthalmology 030104 developmental biology Growth/Differentiation Factor 3 lcsh:RE1-994 symbols Congenital Structural Anomalies business |
| Zdroj: | American Journal of Ophthalmology Case Reports American Journal of Ophthalmology Case Reports, Vol 7, Iss C, Pp 102-106 (2017) |
| ISSN: | 2451-9936 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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