Classical fragile-X phenotype in a female infant disclosed by comprehensive genomic studies
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.16/2273 |
Resumo: | BACKGROUND: We describe a female infant with Fragile-X syndrome, with a fully expanded FMR1 allele and preferential inactivation of the homologous X-chromosome carrying a de novo deletion. This unusual and rare case demonstrates the importance of a detailed genomic approach, the absence of which could be misguiding, and calls for reflection on the current clinical and diagnostic workup for developmental disabilities. CASE PRESENTATION: We present a female infant, referred for genetic testing due to psychomotor developmental delay without specific dysmorphic features or relevant family history. FMR1 mutation screening revealed a methylated full mutation and a normal but inactive FMR1 allele, which led to further investigation. Complete skewing of X-chromosome inactivation towards the paternally-inherited normal-sized FMR1 allele was found. No pathogenic variants were identified in the XIST promoter. Microarray analysis revealed a 439 kb deletion at Xq28, in a region known to be associated with extreme skewing of X-chromosome inactivation. CONCLUSIONS: Overall results enable us to conclude that the developmental delay is the cumulative result of a methylated FMR1 full mutation on the active X-chromosome and the inactivation of the other homologue carrying the de novo 439 kb deletion. Our findings should be taken into consideration in future guidelines for the diagnostic workup on the diagnosis of intellectual disabilities, particularly in female infant cases. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Classical fragile-X phenotype in a female infant disclosed by comprehensive genomic studiesDevelopmental disabilities in femalesFMR1 methylated full mutationFragile-X syndromeSkewing of X-chromosome inactivationXq28 deletionBACKGROUND: We describe a female infant with Fragile-X syndrome, with a fully expanded FMR1 allele and preferential inactivation of the homologous X-chromosome carrying a de novo deletion. This unusual and rare case demonstrates the importance of a detailed genomic approach, the absence of which could be misguiding, and calls for reflection on the current clinical and diagnostic workup for developmental disabilities. CASE PRESENTATION: We present a female infant, referred for genetic testing due to psychomotor developmental delay without specific dysmorphic features or relevant family history. FMR1 mutation screening revealed a methylated full mutation and a normal but inactive FMR1 allele, which led to further investigation. Complete skewing of X-chromosome inactivation towards the paternally-inherited normal-sized FMR1 allele was found. No pathogenic variants were identified in the XIST promoter. Microarray analysis revealed a 439 kb deletion at Xq28, in a region known to be associated with extreme skewing of X-chromosome inactivation. CONCLUSIONS: Overall results enable us to conclude that the developmental delay is the cumulative result of a methylated FMR1 full mutation on the active X-chromosome and the inactivation of the other homologue carrying the de novo 439 kb deletion. Our findings should be taken into consideration in future guidelines for the diagnostic workup on the diagnosis of intellectual disabilities, particularly in female infant cases.Dr. Paula Jorge received a research grant “Bolsa de Investigação DEFI 2015”, CHP, E.P.E.Repositório Científico do Centro Hospitalar Universitário de Santo AntónioJorge, P.Garcia, E.Gonçalves, A.Marques, I.Maia, N.Rodrigues, B.Santos, H.Fonseca, J.Soares, G.Correia, C.Reis-Lima, M.Cirigliano, V.Santos, R.2019-07-18T09:52:20Z2018-05-102018-05-10T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/2273engBMC Med Genet. 2018 May 10;19(1):741471-235010.1186/s12881-018-0589-6info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-20T10:59:52Zoai:repositorio.chporto.pt:10400.16/2273Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:38:29.608929Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Classical fragile-X phenotype in a female infant disclosed by comprehensive genomic studies |
title |
Classical fragile-X phenotype in a female infant disclosed by comprehensive genomic studies |
spellingShingle |
Classical fragile-X phenotype in a female infant disclosed by comprehensive genomic studies Jorge, P. Developmental disabilities in females FMR1 methylated full mutation Fragile-X syndrome Skewing of X-chromosome inactivation Xq28 deletion |
title_short |
Classical fragile-X phenotype in a female infant disclosed by comprehensive genomic studies |
title_full |
Classical fragile-X phenotype in a female infant disclosed by comprehensive genomic studies |
title_fullStr |
Classical fragile-X phenotype in a female infant disclosed by comprehensive genomic studies |
title_full_unstemmed |
Classical fragile-X phenotype in a female infant disclosed by comprehensive genomic studies |
title_sort |
Classical fragile-X phenotype in a female infant disclosed by comprehensive genomic studies |
author |
Jorge, P. |
author_facet |
Jorge, P. Garcia, E. Gonçalves, A. Marques, I. Maia, N. Rodrigues, B. Santos, H. Fonseca, J. Soares, G. Correia, C. Reis-Lima, M. Cirigliano, V. Santos, R. |
author_role |
author |
author2 |
Garcia, E. Gonçalves, A. Marques, I. Maia, N. Rodrigues, B. Santos, H. Fonseca, J. Soares, G. Correia, C. Reis-Lima, M. Cirigliano, V. Santos, R. |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Centro Hospitalar Universitário de Santo António |
dc.contributor.author.fl_str_mv |
Jorge, P. Garcia, E. Gonçalves, A. Marques, I. Maia, N. Rodrigues, B. Santos, H. Fonseca, J. Soares, G. Correia, C. Reis-Lima, M. Cirigliano, V. Santos, R. |
dc.subject.por.fl_str_mv |
Developmental disabilities in females FMR1 methylated full mutation Fragile-X syndrome Skewing of X-chromosome inactivation Xq28 deletion |
topic |
Developmental disabilities in females FMR1 methylated full mutation Fragile-X syndrome Skewing of X-chromosome inactivation Xq28 deletion |
description |
BACKGROUND: We describe a female infant with Fragile-X syndrome, with a fully expanded FMR1 allele and preferential inactivation of the homologous X-chromosome carrying a de novo deletion. This unusual and rare case demonstrates the importance of a detailed genomic approach, the absence of which could be misguiding, and calls for reflection on the current clinical and diagnostic workup for developmental disabilities. CASE PRESENTATION: We present a female infant, referred for genetic testing due to psychomotor developmental delay without specific dysmorphic features or relevant family history. FMR1 mutation screening revealed a methylated full mutation and a normal but inactive FMR1 allele, which led to further investigation. Complete skewing of X-chromosome inactivation towards the paternally-inherited normal-sized FMR1 allele was found. No pathogenic variants were identified in the XIST promoter. Microarray analysis revealed a 439 kb deletion at Xq28, in a region known to be associated with extreme skewing of X-chromosome inactivation. CONCLUSIONS: Overall results enable us to conclude that the developmental delay is the cumulative result of a methylated FMR1 full mutation on the active X-chromosome and the inactivation of the other homologue carrying the de novo 439 kb deletion. Our findings should be taken into consideration in future guidelines for the diagnostic workup on the diagnosis of intellectual disabilities, particularly in female infant cases. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-05-10 2018-05-10T00:00:00Z 2019-07-18T09:52:20Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.16/2273 |
url |
http://hdl.handle.net/10400.16/2273 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
BMC Med Genet. 2018 May 10;19(1):74 1471-2350 10.1186/s12881-018-0589-6 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133646301429760 |