A novel ABCA12 pathologic variant identified in an Ecuadorian harlequin ichthyosis patient: A step forward in genotype-phenotype correlations

BACKGROUND: Autosomal recessive congenital ichthyoses (ARCI) have been associated with different phenotypes including: harlequin ichthyosis (HI), congenital ichthyosiform erythroderma (CIE), and lamellar ichthyosis (LI). While pathogenic variants in all ARCI genes are associated with LI and CIE phen...

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Autores: Montalván-Suárez, M., Esperón Moldes, Uxía Saraiva, Rodríguez Pazos, Laura, Ordoñez Ugalde, Andrés, Moscoso, F., Ugalde-Noritz, N., Santomé Collazo, Luís, Fachal Vilar, Laura, Tettamanti-Miranda, D., Ruiz, J. C., Ginarte Val, Manuel Javier, Vega Gliemmo, Ana
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/15521
Acceso en línea:https://www.ncbi.nlm.nih.gov/pubmed/30916489
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503032/pdf/MGG3-7-e608.pdf
http://hdl.handle.net/20.500.11940/15521
Access Level:acceso abierto
Palabra clave:FPGMX
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spelling A novel ABCA12 pathologic variant identified in an Ecuadorian harlequin ichthyosis patient: A step forward in genotype-phenotype correlationsMontalván-Suárez, M.Esperón Moldes, Uxía SaraivaRodríguez Pazos, LauraOrdoñez Ugalde, AndrésMoscoso, F.Ugalde-Noritz, N.Santomé Collazo, LuísFachal Vilar, LauraTettamanti-Miranda, D.Ruiz, J. C.Ginarte Val, Manuel JavierVega Gliemmo, AnaFPGMXCHUSCHUVIIDISBACKGROUND: Autosomal recessive congenital ichthyoses (ARCI) have been associated with different phenotypes including: harlequin ichthyosis (HI), congenital ichthyosiform erythroderma (CIE), and lamellar ichthyosis (LI). While pathogenic variants in all ARCI genes are associated with LI and CIE phenotypes, the unique gene associated with HI is ABCA12. In HI, the most severe ARCI form, pathogenic variants in both ABCA12 gene alleles usually have a severe impact on protein function. The presence of at least one non-truncating variant frequently causes a less severe congenital ichthyosis phenotype (LI and CIE). METHODS: We report the case of a 4-year-old Ecuadorian boy with a severe skin disease. Genetic diagnosis was performed by NGS. In silico predictions were performed using Alamut software v2.11. A review of the literature was carried out to identify all patients carrying ABCA12 splice-site and missense variants, and to explore their genotype-phenotype correlations. RESULTS: Genetic testing revealed a nonsense substitution, p.(Arg2204*), and a new missense variant, p.(Val1927Leu), in the ABCA12 gene. After performing in silico analysis and a comprehensive review of the literature, we conclude that p.(Val1927Leu) affects a well conserved residue which could either disturb the protein function or alter the splicing process, both alternatives could explain the severe phenotype of our patient. CONCLUSION: This case expands the spectrum of ABCA12 reported disease-causing variants which is important to unravel genotype-phenotype correlations and highlights the importance of missense variants in the development of HI.2019info:eu-repo/semantics/articlehttps://www.ncbi.nlm.nih.gov/pubmed/30916489https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503032/pdf/MGG3-7-e608.pdfhttp://hdl.handle.net/20.500.11940/15521reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/155212026-06-12T08:40:47Z
dc.title.none.fl_str_mv A novel ABCA12 pathologic variant identified in an Ecuadorian harlequin ichthyosis patient: A step forward in genotype-phenotype correlations
title A novel ABCA12 pathologic variant identified in an Ecuadorian harlequin ichthyosis patient: A step forward in genotype-phenotype correlations
spellingShingle A novel ABCA12 pathologic variant identified in an Ecuadorian harlequin ichthyosis patient: A step forward in genotype-phenotype correlations
Montalván-Suárez, M.
FPGMX
CHUS
CHUVI
IDIS
title_short A novel ABCA12 pathologic variant identified in an Ecuadorian harlequin ichthyosis patient: A step forward in genotype-phenotype correlations
title_full A novel ABCA12 pathologic variant identified in an Ecuadorian harlequin ichthyosis patient: A step forward in genotype-phenotype correlations
title_fullStr A novel ABCA12 pathologic variant identified in an Ecuadorian harlequin ichthyosis patient: A step forward in genotype-phenotype correlations
title_full_unstemmed A novel ABCA12 pathologic variant identified in an Ecuadorian harlequin ichthyosis patient: A step forward in genotype-phenotype correlations
title_sort A novel ABCA12 pathologic variant identified in an Ecuadorian harlequin ichthyosis patient: A step forward in genotype-phenotype correlations
dc.creator.none.fl_str_mv Montalván-Suárez, M.
Esperón Moldes, Uxía Saraiva
Rodríguez Pazos, Laura
Ordoñez Ugalde, Andrés
Moscoso, F.
Ugalde-Noritz, N.
Santomé Collazo, Luís
Fachal Vilar, Laura
Tettamanti-Miranda, D.
Ruiz, J. C.
Ginarte Val, Manuel Javier
Vega Gliemmo, Ana
author Montalván-Suárez, M.
author_facet Montalván-Suárez, M.
Esperón Moldes, Uxía Saraiva
Rodríguez Pazos, Laura
Ordoñez Ugalde, Andrés
Moscoso, F.
Ugalde-Noritz, N.
Santomé Collazo, Luís
Fachal Vilar, Laura
Tettamanti-Miranda, D.
Ruiz, J. C.
Ginarte Val, Manuel Javier
Vega Gliemmo, Ana
author_role author
author2 Esperón Moldes, Uxía Saraiva
Rodríguez Pazos, Laura
Ordoñez Ugalde, Andrés
Moscoso, F.
Ugalde-Noritz, N.
Santomé Collazo, Luís
Fachal Vilar, Laura
Tettamanti-Miranda, D.
Ruiz, J. C.
Ginarte Val, Manuel Javier
Vega Gliemmo, Ana
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv FPGMX
CHUS
CHUVI
IDIS
topic FPGMX
CHUS
CHUVI
IDIS
description BACKGROUND: Autosomal recessive congenital ichthyoses (ARCI) have been associated with different phenotypes including: harlequin ichthyosis (HI), congenital ichthyosiform erythroderma (CIE), and lamellar ichthyosis (LI). While pathogenic variants in all ARCI genes are associated with LI and CIE phenotypes, the unique gene associated with HI is ABCA12. In HI, the most severe ARCI form, pathogenic variants in both ABCA12 gene alleles usually have a severe impact on protein function. The presence of at least one non-truncating variant frequently causes a less severe congenital ichthyosis phenotype (LI and CIE). METHODS: We report the case of a 4-year-old Ecuadorian boy with a severe skin disease. Genetic diagnosis was performed by NGS. In silico predictions were performed using Alamut software v2.11. A review of the literature was carried out to identify all patients carrying ABCA12 splice-site and missense variants, and to explore their genotype-phenotype correlations. RESULTS: Genetic testing revealed a nonsense substitution, p.(Arg2204*), and a new missense variant, p.(Val1927Leu), in the ABCA12 gene. After performing in silico analysis and a comprehensive review of the literature, we conclude that p.(Val1927Leu) affects a well conserved residue which could either disturb the protein function or alter the splicing process, both alternatives could explain the severe phenotype of our patient. CONCLUSION: This case expands the spectrum of ABCA12 reported disease-causing variants which is important to unravel genotype-phenotype correlations and highlights the importance of missense variants in the development of HI.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://www.ncbi.nlm.nih.gov/pubmed/30916489
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503032/pdf/MGG3-7-e608.pdf
http://hdl.handle.net/20.500.11940/15521
url https://www.ncbi.nlm.nih.gov/pubmed/30916489
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503032/pdf/MGG3-7-e608.pdf
http://hdl.handle.net/20.500.11940/15521
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas
instname:Servizo Galego de Saúde (SERGAS)
instname_str Servizo Galego de Saúde (SERGAS)
reponame_str RUNA. Repositorio da Consellería de Sanidade e Sergas
collection RUNA. Repositorio da Consellería de Sanidade e Sergas
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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