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Biallelic variants in CENPF causing a phenotype distinct from Strømme syndrome

Biallelic loss‐of‐function (LoF) variants in CENPF gene are responsible for Strømme syndrome, a condition presenting with intestinal atresia, anterior ocular chamber anomalies, and microcephaly. Through an international collaboration, four individuals (three males and one female) carrying CENPF bial...

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Autores principales: Cappuccio, Gerarda, Brillante, Simona, Tammaro, Roberta, Pinelli, Michele, De Bernardi, Margherita Lucia, Gensini, Maria Grazia, Bijlsma, Emilia K., Koopmann, Tamara T., Hoffer, Mariette J. V., McDonald, Kimberly, Hendon, Laura G., Douzgou, Sofia, Deshpande, Charulata, D'Arrigo, Stefano, Torella, Annalaura, Nigro, Vincenzo, Franco, Brunella, Brunetti‐Pierri, Nicola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322429/
https://www.ncbi.nlm.nih.gov/pubmed/35488810
http://dx.doi.org/10.1002/ajmg.c.31973
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author Cappuccio, Gerarda
Brillante, Simona
Tammaro, Roberta
Pinelli, Michele
De Bernardi, Margherita Lucia
Gensini, Maria Grazia
Bijlsma, Emilia K.
Koopmann, Tamara T.
Hoffer, Mariette J. V.
McDonald, Kimberly
Hendon, Laura G.
Douzgou, Sofia
Deshpande, Charulata
D'Arrigo, Stefano
Torella, Annalaura
Nigro, Vincenzo
Franco, Brunella
Brunetti‐Pierri, Nicola
author_facet Cappuccio, Gerarda
Brillante, Simona
Tammaro, Roberta
Pinelli, Michele
De Bernardi, Margherita Lucia
Gensini, Maria Grazia
Bijlsma, Emilia K.
Koopmann, Tamara T.
Hoffer, Mariette J. V.
McDonald, Kimberly
Hendon, Laura G.
Douzgou, Sofia
Deshpande, Charulata
D'Arrigo, Stefano
Torella, Annalaura
Nigro, Vincenzo
Franco, Brunella
Brunetti‐Pierri, Nicola
author_sort Cappuccio, Gerarda
collection PubMed
description Biallelic loss‐of‐function (LoF) variants in CENPF gene are responsible for Strømme syndrome, a condition presenting with intestinal atresia, anterior ocular chamber anomalies, and microcephaly. Through an international collaboration, four individuals (three males and one female) carrying CENPF biallelic variants, including two missense variants in homozygous state and four LoF variants, were identified by exome sequencing. All individuals had variable degree of developmental delay/intellectual disability and microcephaly (ranging from −2.9 SDS to −5.6 SDS) and a recognizable pattern of dysmorphic facial features including inverted‐V shaped interrupted eyebrows, epicanthal fold, depressed nasal bridge, and pointed chin. Although one of the cases had duodenal atresia, all four individuals did not have the combination of internal organ malformations of Strømme syndrome (intestinal atresia and anterior eye segment abnormalities). Immunofluorescence analysis on skin fibroblasts on one of the four cases with the antibody for ARL13B that decorates primary cilia revealed shorter primary cilia that are consistent with a ciliary defect. This case‐series of individuals with biallelic CENPF variants suggests the spectrum of clinical manifestations of the disorder that may be related to CENPF variants is broad and can include phenotypes lacking the cardinal features of Strømme syndrome.
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spelling pubmed-93224292022-07-30 Biallelic variants in CENPF causing a phenotype distinct from Strømme syndrome Cappuccio, Gerarda Brillante, Simona Tammaro, Roberta Pinelli, Michele De Bernardi, Margherita Lucia Gensini, Maria Grazia Bijlsma, Emilia K. Koopmann, Tamara T. Hoffer, Mariette J. V. McDonald, Kimberly Hendon, Laura G. Douzgou, Sofia Deshpande, Charulata D'Arrigo, Stefano Torella, Annalaura Nigro, Vincenzo Franco, Brunella Brunetti‐Pierri, Nicola Am J Med Genet C Semin Med Genet Research Articles Biallelic loss‐of‐function (LoF) variants in CENPF gene are responsible for Strømme syndrome, a condition presenting with intestinal atresia, anterior ocular chamber anomalies, and microcephaly. Through an international collaboration, four individuals (three males and one female) carrying CENPF biallelic variants, including two missense variants in homozygous state and four LoF variants, were identified by exome sequencing. All individuals had variable degree of developmental delay/intellectual disability and microcephaly (ranging from −2.9 SDS to −5.6 SDS) and a recognizable pattern of dysmorphic facial features including inverted‐V shaped interrupted eyebrows, epicanthal fold, depressed nasal bridge, and pointed chin. Although one of the cases had duodenal atresia, all four individuals did not have the combination of internal organ malformations of Strømme syndrome (intestinal atresia and anterior eye segment abnormalities). Immunofluorescence analysis on skin fibroblasts on one of the four cases with the antibody for ARL13B that decorates primary cilia revealed shorter primary cilia that are consistent with a ciliary defect. This case‐series of individuals with biallelic CENPF variants suggests the spectrum of clinical manifestations of the disorder that may be related to CENPF variants is broad and can include phenotypes lacking the cardinal features of Strømme syndrome. John Wiley & Sons, Inc. 2022-04-30 2022-03 /pmc/articles/PMC9322429/ /pubmed/35488810 http://dx.doi.org/10.1002/ajmg.c.31973 Text en © 2022 The Authors. American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Cappuccio, Gerarda
Brillante, Simona
Tammaro, Roberta
Pinelli, Michele
De Bernardi, Margherita Lucia
Gensini, Maria Grazia
Bijlsma, Emilia K.
Koopmann, Tamara T.
Hoffer, Mariette J. V.
McDonald, Kimberly
Hendon, Laura G.
Douzgou, Sofia
Deshpande, Charulata
D'Arrigo, Stefano
Torella, Annalaura
Nigro, Vincenzo
Franco, Brunella
Brunetti‐Pierri, Nicola
Biallelic variants in CENPF causing a phenotype distinct from Strømme syndrome
title Biallelic variants in CENPF causing a phenotype distinct from Strømme syndrome
title_full Biallelic variants in CENPF causing a phenotype distinct from Strømme syndrome
title_fullStr Biallelic variants in CENPF causing a phenotype distinct from Strømme syndrome
title_full_unstemmed Biallelic variants in CENPF causing a phenotype distinct from Strømme syndrome
title_short Biallelic variants in CENPF causing a phenotype distinct from Strømme syndrome
title_sort biallelic variants in cenpf causing a phenotype distinct from strømme syndrome
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322429/
https://www.ncbi.nlm.nih.gov/pubmed/35488810
http://dx.doi.org/10.1002/ajmg.c.31973
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