Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome

Background: Temple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal expressed genes and a silencing the paternally expressed genes in the 14q32 imprinted domain. Classical TS14 phenotypic f...

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Autores: Baena Díez, Neus|||0000-0003-0677-240X, Monk, David, Aguilera, Cinthia|||0000-0002-0363-8590, Fraga, Mario F., Fernández, Agustín F.|||0000-0002-3792-4085, Gabau, Elisabeth|||0000-0001-8120-7393, Corripio, Raquel|||0000-0003-3344-8269, Capdevila, Nuria, Trujillo-Quintero, Juan Pablo|||0000-0001-5901-9388, Ruiz, Anna|||0000-0001-7314-5962, Guitart, Miriam|||0000-0001-5438-8782
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:311731
Acceso en línea:https://ddd.uab.cat/record/311731
https://dx.doi.org/urn:doi:10.1186/s13148-024-01652-8
Access Level:acceso abierto
Palabra clave:DLK1
DMR
Deletion
Methylation
Temple syndrome (TS14)
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spelling Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndromeBaena Díez, Neus|||0000-0003-0677-240XMonk, DavidAguilera, Cinthia|||0000-0002-0363-8590Fraga, Mario F.Fernández, Agustín F.|||0000-0002-3792-4085Gabau, Elisabeth|||0000-0001-8120-7393Corripio, Raquel|||0000-0003-3344-8269Capdevila, NuriaTrujillo-Quintero, Juan Pablo|||0000-0001-5901-9388Ruiz, Anna|||0000-0001-7314-5962Guitart, Miriam|||0000-0001-5438-8782DLK1DMRDeletionMethylationTemple syndrome (TS14)Background: Temple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal expressed genes and a silencing the paternally expressed genes in the 14q32 imprinted domain. Classical TS14 phenotypic features include pre- and postnatal short stature, small hands and feet, muscular hypotonia, motor delay, feeding difficulties, weight gain, premature puberty along and precocious puberty. Methods: An exon array comparative genomic hybridization was performed on a patient affected by psychomotor and language delay, muscular hypotonia, relative macrocephaly, and small hand and feet at two years old. At 6 years of age, the proband presented with precocious thelarche. Genes dosage and methylation within the 14q32 region were analyzed by MS-MLPA. Bisulfite PCR and pyrosequencing were employed to quantification methylation at the four known imprinted differentially methylated regions (DMR) within the 14q32 domain: DLK1 DMR, IG-DMR, MEG3 DMR and MEG8 DMR. Results: The patient had inherited a 69 Kb deletion, encompassing the entire DLK1 gene, on the paternal allele. Relative hypermethylation of the two maternally methylated intervals, DLK1 and MEG8 DMRs, was observed along with normal methylation level at IG-DMR and MEG3 DMR, resulting in a phenotype consistent with TS14. Additional family members with the deletion showed modest methylation changes at both the DLK1 and MEG8 DMRs consistent with parental transmission. Conclusion: We describe a girl with clinical presentation suggestive of Temple syndrome resulting from a small paternal 14q32 deletion that led to DLK1 whole-gene deletion, as well as hypermethylation of the maternally methylated DLK1-DMR.Universitat Autònoma de Barcelona 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/311731https://dx.doi.org/urn:doi:10.1186/s13148-024-01652-8reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3117312026-06-06T12:50:31Z
dc.title.none.fl_str_mv Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
title Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
spellingShingle Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
Baena Díez, Neus|||0000-0003-0677-240X
DLK1
DMR
Deletion
Methylation
Temple syndrome (TS14)
title_short Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
title_full Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
title_fullStr Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
title_full_unstemmed Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
title_sort Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
dc.creator.none.fl_str_mv Baena Díez, Neus|||0000-0003-0677-240X
Monk, David
Aguilera, Cinthia|||0000-0002-0363-8590
Fraga, Mario F.
Fernández, Agustín F.|||0000-0002-3792-4085
Gabau, Elisabeth|||0000-0001-8120-7393
Corripio, Raquel|||0000-0003-3344-8269
Capdevila, Nuria
Trujillo-Quintero, Juan Pablo|||0000-0001-5901-9388
Ruiz, Anna|||0000-0001-7314-5962
Guitart, Miriam|||0000-0001-5438-8782
author Baena Díez, Neus|||0000-0003-0677-240X
author_facet Baena Díez, Neus|||0000-0003-0677-240X
Monk, David
Aguilera, Cinthia|||0000-0002-0363-8590
Fraga, Mario F.
Fernández, Agustín F.|||0000-0002-3792-4085
Gabau, Elisabeth|||0000-0001-8120-7393
Corripio, Raquel|||0000-0003-3344-8269
Capdevila, Nuria
Trujillo-Quintero, Juan Pablo|||0000-0001-5901-9388
Ruiz, Anna|||0000-0001-7314-5962
Guitart, Miriam|||0000-0001-5438-8782
author_role author
author2 Monk, David
Aguilera, Cinthia|||0000-0002-0363-8590
Fraga, Mario F.
Fernández, Agustín F.|||0000-0002-3792-4085
Gabau, Elisabeth|||0000-0001-8120-7393
Corripio, Raquel|||0000-0003-3344-8269
Capdevila, Nuria
Trujillo-Quintero, Juan Pablo|||0000-0001-5901-9388
Ruiz, Anna|||0000-0001-7314-5962
Guitart, Miriam|||0000-0001-5438-8782
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv DLK1
DMR
Deletion
Methylation
Temple syndrome (TS14)
topic DLK1
DMR
Deletion
Methylation
Temple syndrome (TS14)
description Background: Temple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal expressed genes and a silencing the paternally expressed genes in the 14q32 imprinted domain. Classical TS14 phenotypic features include pre- and postnatal short stature, small hands and feet, muscular hypotonia, motor delay, feeding difficulties, weight gain, premature puberty along and precocious puberty. Methods: An exon array comparative genomic hybridization was performed on a patient affected by psychomotor and language delay, muscular hypotonia, relative macrocephaly, and small hand and feet at two years old. At 6 years of age, the proband presented with precocious thelarche. Genes dosage and methylation within the 14q32 region were analyzed by MS-MLPA. Bisulfite PCR and pyrosequencing were employed to quantification methylation at the four known imprinted differentially methylated regions (DMR) within the 14q32 domain: DLK1 DMR, IG-DMR, MEG3 DMR and MEG8 DMR. Results: The patient had inherited a 69 Kb deletion, encompassing the entire DLK1 gene, on the paternal allele. Relative hypermethylation of the two maternally methylated intervals, DLK1 and MEG8 DMRs, was observed along with normal methylation level at IG-DMR and MEG3 DMR, resulting in a phenotype consistent with TS14. Additional family members with the deletion showed modest methylation changes at both the DLK1 and MEG8 DMRs consistent with parental transmission. Conclusion: We describe a girl with clinical presentation suggestive of Temple syndrome resulting from a small paternal 14q32 deletion that led to DLK1 whole-gene deletion, as well as hypermethylation of the maternally methylated DLK1-DMR.
publishDate 2024
dc.date.none.fl_str_mv 2
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/311731
https://dx.doi.org/urn:doi:10.1186/s13148-024-01652-8
url https://ddd.uab.cat/record/311731
https://dx.doi.org/urn:doi:10.1186/s13148-024-01652-8
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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