TP63‐mutation as a cause of prenatal lethal multicystic dysplastic kidneys
Abstract Background Ectrodactyly‐ectodermal dysplasia‐clefting syndrome 3 (EEC) is one of the six overlapping syndromes caused by mutations in the tumor protein p63 gene (TP63). EEC is suspected when patients have cleft hands or feet, polydactyly, and syndactyly, abnormal development of the ectoderm...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-11-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1486 |
| _version_ | 1797301007721431040 |
|---|---|
| author | Isabel Friedmann Carla Campagnolo Nancy Chan Ghislain Hardy Maha Saleh |
| author_facet | Isabel Friedmann Carla Campagnolo Nancy Chan Ghislain Hardy Maha Saleh |
| author_sort | Isabel Friedmann |
| collection | DOAJ |
| description | Abstract Background Ectrodactyly‐ectodermal dysplasia‐clefting syndrome 3 (EEC) is one of the six overlapping syndromes caused by mutations in the tumor protein p63 gene (TP63). EEC is suspected when patients have cleft hands or feet, polydactyly, and syndactyly, abnormal development of the ectodermally derived structures, and orofacial clefting. Genitourinary (GU) anomalies have been identified in patients with EEC, yet these are often under‐recognized and under‐reported. The available literature on sonographic prenatal findings is sparse, especially when considering GU anomalies. Methods We present the case of a male stillborn fetus, who was found antenatally to have multicystic dysplastic kidneys and anhydramnios. Following the termination of pregnancy, examination and autopsy further revealed unilateral polydactyly and bilateral syndactyly which had not been previously identified on antenatal ultrasound. Results Whole‐exome sequencing (WES) revealed a de novo heterozygous pathogenic variant in exon 5 of the TP63 gene: p.His247Arg: c.740A>G (NM_003722.4) which has been reported in the literature. The His247Arg variant has been published as a pathogenic variant in association with EEC, both with and without orofacial clefting. Conclusion Our prenatal case expands the phenotypic spectrum of TP63‐related disorders in general. In addition, it adds to the phenotype associated with the His247Arg pathogenic variant responsible for EEC. Further, we highlight the importance of WES as a postnatal tool to help clarify unexpected findings, and as a way to add to the spectrum of existing phenotypes of known single‐gene disorders. |
| first_indexed | 2024-03-07T23:16:07Z |
| format | Article |
| id | doaj.art-987c96a1f34042ce87929a5b50ae5770 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:16:07Z |
| publishDate | 2020-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-987c96a1f34042ce87929a5b50ae57702024-02-21T11:47:10ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-11-01811n/an/a10.1002/mgg3.1486TP63‐mutation as a cause of prenatal lethal multicystic dysplastic kidneysIsabel Friedmann0Carla Campagnolo1Nancy Chan2Ghislain Hardy3Maha Saleh4Schulich School of Medicine and Dentistry University of Western Ontario London ON CanadaDivision of Genetics and Metabolism Department of Paediatrics London Health Sciences Centre London ON CanadaSchulich School of Medicine and Dentistry University of Western Ontario London ON CanadaSchulich School of Medicine and Dentistry University of Western Ontario London ON CanadaSchulich School of Medicine and Dentistry University of Western Ontario London ON CanadaAbstract Background Ectrodactyly‐ectodermal dysplasia‐clefting syndrome 3 (EEC) is one of the six overlapping syndromes caused by mutations in the tumor protein p63 gene (TP63). EEC is suspected when patients have cleft hands or feet, polydactyly, and syndactyly, abnormal development of the ectodermally derived structures, and orofacial clefting. Genitourinary (GU) anomalies have been identified in patients with EEC, yet these are often under‐recognized and under‐reported. The available literature on sonographic prenatal findings is sparse, especially when considering GU anomalies. Methods We present the case of a male stillborn fetus, who was found antenatally to have multicystic dysplastic kidneys and anhydramnios. Following the termination of pregnancy, examination and autopsy further revealed unilateral polydactyly and bilateral syndactyly which had not been previously identified on antenatal ultrasound. Results Whole‐exome sequencing (WES) revealed a de novo heterozygous pathogenic variant in exon 5 of the TP63 gene: p.His247Arg: c.740A>G (NM_003722.4) which has been reported in the literature. The His247Arg variant has been published as a pathogenic variant in association with EEC, both with and without orofacial clefting. Conclusion Our prenatal case expands the phenotypic spectrum of TP63‐related disorders in general. In addition, it adds to the phenotype associated with the His247Arg pathogenic variant responsible for EEC. Further, we highlight the importance of WES as a postnatal tool to help clarify unexpected findings, and as a way to add to the spectrum of existing phenotypes of known single‐gene disorders.https://doi.org/10.1002/mgg3.1486antenatal ultrasoundectrodactyly‐ectodermal dysplasia‐clefting syndrome 3renal dysplasiatumor protein p63whole‐exome sequencing |
| spellingShingle | Isabel Friedmann Carla Campagnolo Nancy Chan Ghislain Hardy Maha Saleh TP63‐mutation as a cause of prenatal lethal multicystic dysplastic kidneys Molecular Genetics & Genomic Medicine antenatal ultrasound ectrodactyly‐ectodermal dysplasia‐clefting syndrome 3 renal dysplasia tumor protein p63 whole‐exome sequencing |
| title | TP63‐mutation as a cause of prenatal lethal multicystic dysplastic kidneys |
| title_full | TP63‐mutation as a cause of prenatal lethal multicystic dysplastic kidneys |
| title_fullStr | TP63‐mutation as a cause of prenatal lethal multicystic dysplastic kidneys |
| title_full_unstemmed | TP63‐mutation as a cause of prenatal lethal multicystic dysplastic kidneys |
| title_short | TP63‐mutation as a cause of prenatal lethal multicystic dysplastic kidneys |
| title_sort | tp63 mutation as a cause of prenatal lethal multicystic dysplastic kidneys |
| topic | antenatal ultrasound ectrodactyly‐ectodermal dysplasia‐clefting syndrome 3 renal dysplasia tumor protein p63 whole‐exome sequencing |
| url | https://doi.org/10.1002/mgg3.1486 |
| work_keys_str_mv | AT isabelfriedmann tp63mutationasacauseofprenatallethalmulticysticdysplastickidneys AT carlacampagnolo tp63mutationasacauseofprenatallethalmulticysticdysplastickidneys AT nancychan tp63mutationasacauseofprenatallethalmulticysticdysplastickidneys AT ghislainhardy tp63mutationasacauseofprenatallethalmulticysticdysplastickidneys AT mahasaleh tp63mutationasacauseofprenatallethalmulticysticdysplastickidneys |