Cargando…

Case Report: Partial Uniparental Disomy Unmasks a Novel Recessive Mutation in the LYST Gene in a Patient With a Severe Phenotype of Chédiak-Higashi Syndrome

Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive (AR) immune disorder that has usually been associated to missense, nonsense or indels mutations in the LYST gene. In this study, we describe for the first time the case of a CHS patient carrying a homozygous mutation in the LYST gene inher...

Descripción completa

Detalles Bibliográficos
Autores principales: Boluda-Navarro, Mireia, Ibáñez, Mariam, Liquori, Alessandro, Franco-Jarava, Clara, Martínez-Gallo, Mónica, Rodríguez-Vega, Héctor, Teresa, Jaijo, Carreras, Carmen, Such, Esperanza, Zúñiga, Ángel, Colobran, Roger, Cervera, José Vicente
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044466/
https://www.ncbi.nlm.nih.gov/pubmed/33868243
http://dx.doi.org/10.3389/fimmu.2021.625591
_version_ 1783678491714125824
author Boluda-Navarro, Mireia
Ibáñez, Mariam
Liquori, Alessandro
Franco-Jarava, Clara
Martínez-Gallo, Mónica
Rodríguez-Vega, Héctor
Teresa, Jaijo
Carreras, Carmen
Such, Esperanza
Zúñiga, Ángel
Colobran, Roger
Cervera, José Vicente
author_facet Boluda-Navarro, Mireia
Ibáñez, Mariam
Liquori, Alessandro
Franco-Jarava, Clara
Martínez-Gallo, Mónica
Rodríguez-Vega, Héctor
Teresa, Jaijo
Carreras, Carmen
Such, Esperanza
Zúñiga, Ángel
Colobran, Roger
Cervera, José Vicente
author_sort Boluda-Navarro, Mireia
collection PubMed
description Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive (AR) immune disorder that has usually been associated to missense, nonsense or indels mutations in the LYST gene. In this study, we describe for the first time the case of a CHS patient carrying a homozygous mutation in the LYST gene inherited as a result of a partial uniparental isodisomy (UPiD) of maternal origin. Sanger sequencing of the LYST cDNA and single nucleotide polymorphism (SNP)-arrays were performed to identify the causative mutation and to explain the molecular mechanism of inheritance, respectively. Partial-UPiD leads to a copy neutral loss of heterozygosity (CN-LOH) of the telomeric region of chromosome 1 (1q41q44), unmasking the potential effect of the mutation detected. The mutation (c.8380dupT) is an insertion located in exon 32 of the LYST gene resulting in a premature stop codon and leading to the loss of all the conserved domains at the C-terminal of the LYST protein. This would account for the severe phenotype observed. We also reviewed the only two previously reported cases of CHS as a result of a uniparental disomy. In this study, we show that the combination of different strategies, including the use of SNP-arrays, is pivotal to fine-tune the diagnosis of rare AR disorders, such as CHS. Moreover, this case highlights the relevance of uniparental disomy as a potential mechanism of CHS expression in non-consanguineous families.
format Online
Article
Text
id pubmed-8044466
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-80444662021-04-15 Case Report: Partial Uniparental Disomy Unmasks a Novel Recessive Mutation in the LYST Gene in a Patient With a Severe Phenotype of Chédiak-Higashi Syndrome Boluda-Navarro, Mireia Ibáñez, Mariam Liquori, Alessandro Franco-Jarava, Clara Martínez-Gallo, Mónica Rodríguez-Vega, Héctor Teresa, Jaijo Carreras, Carmen Such, Esperanza Zúñiga, Ángel Colobran, Roger Cervera, José Vicente Front Immunol Immunology Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive (AR) immune disorder that has usually been associated to missense, nonsense or indels mutations in the LYST gene. In this study, we describe for the first time the case of a CHS patient carrying a homozygous mutation in the LYST gene inherited as a result of a partial uniparental isodisomy (UPiD) of maternal origin. Sanger sequencing of the LYST cDNA and single nucleotide polymorphism (SNP)-arrays were performed to identify the causative mutation and to explain the molecular mechanism of inheritance, respectively. Partial-UPiD leads to a copy neutral loss of heterozygosity (CN-LOH) of the telomeric region of chromosome 1 (1q41q44), unmasking the potential effect of the mutation detected. The mutation (c.8380dupT) is an insertion located in exon 32 of the LYST gene resulting in a premature stop codon and leading to the loss of all the conserved domains at the C-terminal of the LYST protein. This would account for the severe phenotype observed. We also reviewed the only two previously reported cases of CHS as a result of a uniparental disomy. In this study, we show that the combination of different strategies, including the use of SNP-arrays, is pivotal to fine-tune the diagnosis of rare AR disorders, such as CHS. Moreover, this case highlights the relevance of uniparental disomy as a potential mechanism of CHS expression in non-consanguineous families. Frontiers Media S.A. 2021-03-31 /pmc/articles/PMC8044466/ /pubmed/33868243 http://dx.doi.org/10.3389/fimmu.2021.625591 Text en Copyright © 2021 Boluda-Navarro, Ibáñez, Liquori, Franco-Jarava, Martínez-Gallo, Rodríguez-Vega, Teresa, Carreras, Such, Zúñiga, Colobran and Cervera https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Boluda-Navarro, Mireia
Ibáñez, Mariam
Liquori, Alessandro
Franco-Jarava, Clara
Martínez-Gallo, Mónica
Rodríguez-Vega, Héctor
Teresa, Jaijo
Carreras, Carmen
Such, Esperanza
Zúñiga, Ángel
Colobran, Roger
Cervera, José Vicente
Case Report: Partial Uniparental Disomy Unmasks a Novel Recessive Mutation in the LYST Gene in a Patient With a Severe Phenotype of Chédiak-Higashi Syndrome
title Case Report: Partial Uniparental Disomy Unmasks a Novel Recessive Mutation in the LYST Gene in a Patient With a Severe Phenotype of Chédiak-Higashi Syndrome
title_full Case Report: Partial Uniparental Disomy Unmasks a Novel Recessive Mutation in the LYST Gene in a Patient With a Severe Phenotype of Chédiak-Higashi Syndrome
title_fullStr Case Report: Partial Uniparental Disomy Unmasks a Novel Recessive Mutation in the LYST Gene in a Patient With a Severe Phenotype of Chédiak-Higashi Syndrome
title_full_unstemmed Case Report: Partial Uniparental Disomy Unmasks a Novel Recessive Mutation in the LYST Gene in a Patient With a Severe Phenotype of Chédiak-Higashi Syndrome
title_short Case Report: Partial Uniparental Disomy Unmasks a Novel Recessive Mutation in the LYST Gene in a Patient With a Severe Phenotype of Chédiak-Higashi Syndrome
title_sort case report: partial uniparental disomy unmasks a novel recessive mutation in the lyst gene in a patient with a severe phenotype of chédiak-higashi syndrome
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044466/
https://www.ncbi.nlm.nih.gov/pubmed/33868243
http://dx.doi.org/10.3389/fimmu.2021.625591
work_keys_str_mv AT boludanavarromireia casereportpartialuniparentaldisomyunmasksanovelrecessivemutationinthelystgeneinapatientwithaseverephenotypeofchediakhigashisyndrome
AT ibanezmariam casereportpartialuniparentaldisomyunmasksanovelrecessivemutationinthelystgeneinapatientwithaseverephenotypeofchediakhigashisyndrome
AT liquorialessandro casereportpartialuniparentaldisomyunmasksanovelrecessivemutationinthelystgeneinapatientwithaseverephenotypeofchediakhigashisyndrome
AT francojaravaclara casereportpartialuniparentaldisomyunmasksanovelrecessivemutationinthelystgeneinapatientwithaseverephenotypeofchediakhigashisyndrome
AT martinezgallomonica casereportpartialuniparentaldisomyunmasksanovelrecessivemutationinthelystgeneinapatientwithaseverephenotypeofchediakhigashisyndrome
AT rodriguezvegahector casereportpartialuniparentaldisomyunmasksanovelrecessivemutationinthelystgeneinapatientwithaseverephenotypeofchediakhigashisyndrome
AT teresajaijo casereportpartialuniparentaldisomyunmasksanovelrecessivemutationinthelystgeneinapatientwithaseverephenotypeofchediakhigashisyndrome
AT carrerascarmen casereportpartialuniparentaldisomyunmasksanovelrecessivemutationinthelystgeneinapatientwithaseverephenotypeofchediakhigashisyndrome
AT suchesperanza casereportpartialuniparentaldisomyunmasksanovelrecessivemutationinthelystgeneinapatientwithaseverephenotypeofchediakhigashisyndrome
AT zunigaangel casereportpartialuniparentaldisomyunmasksanovelrecessivemutationinthelystgeneinapatientwithaseverephenotypeofchediakhigashisyndrome
AT colobranroger casereportpartialuniparentaldisomyunmasksanovelrecessivemutationinthelystgeneinapatientwithaseverephenotypeofchediakhigashisyndrome
AT cerverajosevicente casereportpartialuniparentaldisomyunmasksanovelrecessivemutationinthelystgeneinapatientwithaseverephenotypeofchediakhigashisyndrome