Preimplantation genetic testing for a chr14q32 microdeletion in a family with Kagami-Ogata syndrome and Temple syndrome

Introduction Kagami-Ogata syndrome (KOS14) and Temple syndrome (TS14) are two disorders associated with reciprocal alterations within the chr14q32 imprinted domain. Here, we present a work-up strategy for preimplantation genetic testing (PGT) to avoid the transmission of a causative micro-deletion....

Descripción completa

Detalles Bibliográficos
Autores: Sabria-Back J, Monteagudo-Sánchez A, Sánchez-Delgado M, Ferguson-Smith AC, Gómez O, Pertierra Cartada A, Tenorio J, Nevado J, Lapunzina P, Pereda Aguirre A, Giménez Sevilla C, Toro Toro E, Perez de Nanclares G, Monk D
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p19083
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19083
Access Level:acceso abierto
Palabra clave:DNA methylation
epigenomics
id ES_e69e5ccc6c4ff6c53c86efdb0c07df11
oai_identifier_str oai:fsjd.fundanetsuite.com:p19083
network_acronym_str ES
network_name_str España
repository_id_str
spelling Preimplantation genetic testing for a chr14q32 microdeletion in a family with Kagami-Ogata syndrome and Temple syndromeSabria-Back JMonteagudo-Sánchez ASánchez-Delgado MFerguson-Smith ACGómez OPertierra Cartada ATenorio JNevado JLapunzina PPereda Aguirre AGiménez Sevilla CToro Toro EPerez de Nanclares GMonk DDNA methylationepigenomicsIntroduction Kagami-Ogata syndrome (KOS14) and Temple syndrome (TS14) are two disorders associated with reciprocal alterations within the chr14q32 imprinted domain. Here, we present a work-up strategy for preimplantation genetic testing (PGT) to avoid the transmission of a causative micro-deletion. Methods We analysed DNA from the KOS14 index case and parents using methylation-sensitive ligation-mediated probe amplification and methylation pyrosequencing. The extent of the deletion was mapped using SNP arrays. PGT was performed in trophectoderm samples in order to identify unaffected embryos. Samples were amplified using multiple displacement amplification, followed by genome-wide SNP genotyping to determine the at-risk haplotype and next-generation sequencing to determine aneuploidies. Results A fully methylated pattern at the normally paternally methylated IG-DMR and MEG3 DMR in the KOS14 proband, accompanied by an unmethylated profile in the TS14 mother was consistent with maternal and paternal transmission of a deletion, respectively. Further analysis revealed a 108 kb deletion in both cases. The inheritance of the deletion on different parental alleles was consistent with the opposing phenotypes. In vitro fertilisation with intracytoplasmatic sperm injection and PGT were used to screen for deletion status and to transfer an unaffected embryo in this couple. A single euploid-unaffected embryo was identified resulting in a healthy baby born. Discussion We identify a microdeletion responsible for multigeneration KOS14 and TS14 within a single family where carriers have a 50% risk of transmitting the deletion to their offspring. We show that PGT can successfully be offered to couples with IDs caused by genetic anomalies.BMJ PUBLISHING GROUP2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19083JOURNAL OF MEDICAL GENETICSISSN: 00222593ISSNe: 14686244reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p190832026-05-27T12:37:41Z
dc.title.none.fl_str_mv Preimplantation genetic testing for a chr14q32 microdeletion in a family with Kagami-Ogata syndrome and Temple syndrome
title Preimplantation genetic testing for a chr14q32 microdeletion in a family with Kagami-Ogata syndrome and Temple syndrome
spellingShingle Preimplantation genetic testing for a chr14q32 microdeletion in a family with Kagami-Ogata syndrome and Temple syndrome
Sabria-Back J
DNA methylation
epigenomics
title_short Preimplantation genetic testing for a chr14q32 microdeletion in a family with Kagami-Ogata syndrome and Temple syndrome
title_full Preimplantation genetic testing for a chr14q32 microdeletion in a family with Kagami-Ogata syndrome and Temple syndrome
title_fullStr Preimplantation genetic testing for a chr14q32 microdeletion in a family with Kagami-Ogata syndrome and Temple syndrome
title_full_unstemmed Preimplantation genetic testing for a chr14q32 microdeletion in a family with Kagami-Ogata syndrome and Temple syndrome
title_sort Preimplantation genetic testing for a chr14q32 microdeletion in a family with Kagami-Ogata syndrome and Temple syndrome
dc.creator.none.fl_str_mv Sabria-Back J
Monteagudo-Sánchez A
Sánchez-Delgado M
Ferguson-Smith AC
Gómez O
Pertierra Cartada A
Tenorio J
Nevado J
Lapunzina P
Pereda Aguirre A
Giménez Sevilla C
Toro Toro E
Perez de Nanclares G
Monk D
author Sabria-Back J
author_facet Sabria-Back J
Monteagudo-Sánchez A
Sánchez-Delgado M
Ferguson-Smith AC
Gómez O
Pertierra Cartada A
Tenorio J
Nevado J
Lapunzina P
Pereda Aguirre A
Giménez Sevilla C
Toro Toro E
Perez de Nanclares G
Monk D
author_role author
author2 Monteagudo-Sánchez A
Sánchez-Delgado M
Ferguson-Smith AC
Gómez O
Pertierra Cartada A
Tenorio J
Nevado J
Lapunzina P
Pereda Aguirre A
Giménez Sevilla C
Toro Toro E
Perez de Nanclares G
Monk D
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DNA methylation
epigenomics
topic DNA methylation
epigenomics
description Introduction Kagami-Ogata syndrome (KOS14) and Temple syndrome (TS14) are two disorders associated with reciprocal alterations within the chr14q32 imprinted domain. Here, we present a work-up strategy for preimplantation genetic testing (PGT) to avoid the transmission of a causative micro-deletion. Methods We analysed DNA from the KOS14 index case and parents using methylation-sensitive ligation-mediated probe amplification and methylation pyrosequencing. The extent of the deletion was mapped using SNP arrays. PGT was performed in trophectoderm samples in order to identify unaffected embryos. Samples were amplified using multiple displacement amplification, followed by genome-wide SNP genotyping to determine the at-risk haplotype and next-generation sequencing to determine aneuploidies. Results A fully methylated pattern at the normally paternally methylated IG-DMR and MEG3 DMR in the KOS14 proband, accompanied by an unmethylated profile in the TS14 mother was consistent with maternal and paternal transmission of a deletion, respectively. Further analysis revealed a 108 kb deletion in both cases. The inheritance of the deletion on different parental alleles was consistent with the opposing phenotypes. In vitro fertilisation with intracytoplasmatic sperm injection and PGT were used to screen for deletion status and to transfer an unaffected embryo in this couple. A single euploid-unaffected embryo was identified resulting in a healthy baby born. Discussion We identify a microdeletion responsible for multigeneration KOS14 and TS14 within a single family where carriers have a 50% risk of transmitting the deletion to their offspring. We show that PGT can successfully be offered to couples with IDs caused by genetic anomalies.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19083
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19083
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BMJ PUBLISHING GROUP
publisher.none.fl_str_mv BMJ PUBLISHING GROUP
dc.source.none.fl_str_mv JOURNAL OF MEDICAL GENETICS
ISSN: 00222593
ISSNe: 14686244
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869422782582882304
score 15,812429

Similares en LA Referencia