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Further expansion and confirmation of phenotype in rare loss of YWHAE gene distinct from Miller–Dieker syndrome
Deletion of 17p13.3 has varying degrees of severity on brain development based on precise location and size of the deletion. The most severe phenotype is Miller–Dieker syndrome (MDS) which is characterized by lissencephaly, dysmorphic facial features, growth failure, developmental disability, and of...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099970/ https://www.ncbi.nlm.nih.gov/pubmed/36433683 http://dx.doi.org/10.1002/ajmg.a.63057 |
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author | Baker, Elizabeth K. Brewer, Casey J. Ferreira, Leonardo Schapiro, Mark Tenney, Jeffrey Wied, Heather M. Kline‐Fath, Beth M. Smolarek, Teresa A. Weaver, K. Nicole Hopkin, Robert J. |
author_facet | Baker, Elizabeth K. Brewer, Casey J. Ferreira, Leonardo Schapiro, Mark Tenney, Jeffrey Wied, Heather M. Kline‐Fath, Beth M. Smolarek, Teresa A. Weaver, K. Nicole Hopkin, Robert J. |
author_sort | Baker, Elizabeth K. |
collection | PubMed |
description | Deletion of 17p13.3 has varying degrees of severity on brain development based on precise location and size of the deletion. The most severe phenotype is Miller–Dieker syndrome (MDS) which is characterized by lissencephaly, dysmorphic facial features, growth failure, developmental disability, and often early death. Haploinsufficiency of PAFAH1B1 is responsible for the characteristic lissencephaly in MDS. The precise role of YWHAE haploinsufficiency in MDS is unclear. Case reports are beginning to elucidate the phenotypes of individuals with 17p13.3 deletions that have deletion of YWHAE but do not include deletion of PAFAH1B1. Through our clinical genetics practice, we identified four individuals with 17p13.3 deletion that include YWHAE but not PAFAH1B1. These patients have a similar phenotype of dysmorphic facial features, developmental delay, and leukoencephalopathy. In a review of the literature, we identified 19 patients with 17p13.3 microdeletion sparing PAFAH1B1 but deleting YWHAE. Haploinsufficiency of YWHAE is associated with brain abnormalities including cystic changes. These individuals have high frequency of epilepsy, intellectual disability, and dysmorphic facial features including prominent forehead, epicanthal folds, and broad nasal root. We conclude that deletion of 17p13.3 excluding PAFAH1B1 but including YWHAE is associated with a consistent phenotype and should be considered a distinct condition from MDS. |
format | Online Article Text |
id | pubmed-10099970 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100999702023-04-14 Further expansion and confirmation of phenotype in rare loss of YWHAE gene distinct from Miller–Dieker syndrome Baker, Elizabeth K. Brewer, Casey J. Ferreira, Leonardo Schapiro, Mark Tenney, Jeffrey Wied, Heather M. Kline‐Fath, Beth M. Smolarek, Teresa A. Weaver, K. Nicole Hopkin, Robert J. Am J Med Genet A Original Articles Deletion of 17p13.3 has varying degrees of severity on brain development based on precise location and size of the deletion. The most severe phenotype is Miller–Dieker syndrome (MDS) which is characterized by lissencephaly, dysmorphic facial features, growth failure, developmental disability, and often early death. Haploinsufficiency of PAFAH1B1 is responsible for the characteristic lissencephaly in MDS. The precise role of YWHAE haploinsufficiency in MDS is unclear. Case reports are beginning to elucidate the phenotypes of individuals with 17p13.3 deletions that have deletion of YWHAE but do not include deletion of PAFAH1B1. Through our clinical genetics practice, we identified four individuals with 17p13.3 deletion that include YWHAE but not PAFAH1B1. These patients have a similar phenotype of dysmorphic facial features, developmental delay, and leukoencephalopathy. In a review of the literature, we identified 19 patients with 17p13.3 microdeletion sparing PAFAH1B1 but deleting YWHAE. Haploinsufficiency of YWHAE is associated with brain abnormalities including cystic changes. These individuals have high frequency of epilepsy, intellectual disability, and dysmorphic facial features including prominent forehead, epicanthal folds, and broad nasal root. We conclude that deletion of 17p13.3 excluding PAFAH1B1 but including YWHAE is associated with a consistent phenotype and should be considered a distinct condition from MDS. John Wiley & Sons, Inc. 2022-11-25 2023-02 /pmc/articles/PMC10099970/ /pubmed/36433683 http://dx.doi.org/10.1002/ajmg.a.63057 Text en © 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Baker, Elizabeth K. Brewer, Casey J. Ferreira, Leonardo Schapiro, Mark Tenney, Jeffrey Wied, Heather M. Kline‐Fath, Beth M. Smolarek, Teresa A. Weaver, K. Nicole Hopkin, Robert J. Further expansion and confirmation of phenotype in rare loss of YWHAE gene distinct from Miller–Dieker syndrome |
title | Further expansion and confirmation of phenotype in rare loss of
YWHAE
gene distinct from Miller–Dieker syndrome |
title_full | Further expansion and confirmation of phenotype in rare loss of
YWHAE
gene distinct from Miller–Dieker syndrome |
title_fullStr | Further expansion and confirmation of phenotype in rare loss of
YWHAE
gene distinct from Miller–Dieker syndrome |
title_full_unstemmed | Further expansion and confirmation of phenotype in rare loss of
YWHAE
gene distinct from Miller–Dieker syndrome |
title_short | Further expansion and confirmation of phenotype in rare loss of
YWHAE
gene distinct from Miller–Dieker syndrome |
title_sort | further expansion and confirmation of phenotype in rare loss of
ywhae
gene distinct from miller–dieker syndrome |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099970/ https://www.ncbi.nlm.nih.gov/pubmed/36433683 http://dx.doi.org/10.1002/ajmg.a.63057 |
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