Cargando…

Association between phenotype and deletion size in 22q11.2 microdeletion syndrome: systematic review and meta-analysis

BACKGROUND: Chromosome 22q11.2 microdeletion syndrome, a disorder caused by heterozygous loss of genetic material in chromosome region 22q11.2, has a broad range of clinical symptoms. The most common congenital anomalies involve the palate in 80% of patients, and the heart in 50–60% of them. The cau...

Descripción completa

Detalles Bibliográficos
Autores principales: Rozas, M. Fernanda, Benavides, Felipe, León, Luis, Repetto, Gabriela M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688301/
https://www.ncbi.nlm.nih.gov/pubmed/31399107
http://dx.doi.org/10.1186/s13023-019-1170-x
_version_ 1783442859627642880
author Rozas, M. Fernanda
Benavides, Felipe
León, Luis
Repetto, Gabriela M.
author_facet Rozas, M. Fernanda
Benavides, Felipe
León, Luis
Repetto, Gabriela M.
author_sort Rozas, M. Fernanda
collection PubMed
description BACKGROUND: Chromosome 22q11.2 microdeletion syndrome, a disorder caused by heterozygous loss of genetic material in chromosome region 22q11.2, has a broad range of clinical symptoms. The most common congenital anomalies involve the palate in 80% of patients, and the heart in 50–60% of them. The cause of the phenotypic variability is unknown. Patients usually harbor one of three common deletions sizes: 3, 2 and 1.5 Mb, between low copy repeats (LCR) designated A-D, A-C and A-B, respectively. This study aimed to analyze the association between these 3 deletion sizes and the presence of congenital cardiac and/or palatal malformations in individuals with this condition. A systematic review and meta-analysis were conducted, merging relevant published studies with data from Chilean patients to increase statistical power. RESULTS: Eight articles out of 432 were included; the data from these studies was merged with our own, achieving a total of 1514 and 487 patients to evaluate cardiac and palate malformations, respectively. None of the compared deleted chromosomal segments were statistically associated with cardiac defects (OR(AB v/s AC-AD): 0.654 [0.408–1.046]; OR (AD v/s AB-AC): 1.291 [0.860–1.939]) or palate anomalies (OR(AB v/s AC-AD): 1.731 [0.708–4.234]; OR (AD v/s AB-AC): 0.628 [0.286–1.382]). CONCLUSIONS: The lack of association between deletion size and CHD or PA found in this meta-analysis suggests that deletion size does not explain the incomplete penetrance of these 2 major manifestations, and that the critical region for the development of heart and palatal abnormalities is within LCR A-B, the smallest region of overlap among the three deletion sizes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13023-019-1170-x) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6688301
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-66883012019-08-14 Association between phenotype and deletion size in 22q11.2 microdeletion syndrome: systematic review and meta-analysis Rozas, M. Fernanda Benavides, Felipe León, Luis Repetto, Gabriela M. Orphanet J Rare Dis Research BACKGROUND: Chromosome 22q11.2 microdeletion syndrome, a disorder caused by heterozygous loss of genetic material in chromosome region 22q11.2, has a broad range of clinical symptoms. The most common congenital anomalies involve the palate in 80% of patients, and the heart in 50–60% of them. The cause of the phenotypic variability is unknown. Patients usually harbor one of three common deletions sizes: 3, 2 and 1.5 Mb, between low copy repeats (LCR) designated A-D, A-C and A-B, respectively. This study aimed to analyze the association between these 3 deletion sizes and the presence of congenital cardiac and/or palatal malformations in individuals with this condition. A systematic review and meta-analysis were conducted, merging relevant published studies with data from Chilean patients to increase statistical power. RESULTS: Eight articles out of 432 were included; the data from these studies was merged with our own, achieving a total of 1514 and 487 patients to evaluate cardiac and palate malformations, respectively. None of the compared deleted chromosomal segments were statistically associated with cardiac defects (OR(AB v/s AC-AD): 0.654 [0.408–1.046]; OR (AD v/s AB-AC): 1.291 [0.860–1.939]) or palate anomalies (OR(AB v/s AC-AD): 1.731 [0.708–4.234]; OR (AD v/s AB-AC): 0.628 [0.286–1.382]). CONCLUSIONS: The lack of association between deletion size and CHD or PA found in this meta-analysis suggests that deletion size does not explain the incomplete penetrance of these 2 major manifestations, and that the critical region for the development of heart and palatal abnormalities is within LCR A-B, the smallest region of overlap among the three deletion sizes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13023-019-1170-x) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-09 /pmc/articles/PMC6688301/ /pubmed/31399107 http://dx.doi.org/10.1186/s13023-019-1170-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Rozas, M. Fernanda
Benavides, Felipe
León, Luis
Repetto, Gabriela M.
Association between phenotype and deletion size in 22q11.2 microdeletion syndrome: systematic review and meta-analysis
title Association between phenotype and deletion size in 22q11.2 microdeletion syndrome: systematic review and meta-analysis
title_full Association between phenotype and deletion size in 22q11.2 microdeletion syndrome: systematic review and meta-analysis
title_fullStr Association between phenotype and deletion size in 22q11.2 microdeletion syndrome: systematic review and meta-analysis
title_full_unstemmed Association between phenotype and deletion size in 22q11.2 microdeletion syndrome: systematic review and meta-analysis
title_short Association between phenotype and deletion size in 22q11.2 microdeletion syndrome: systematic review and meta-analysis
title_sort association between phenotype and deletion size in 22q11.2 microdeletion syndrome: systematic review and meta-analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688301/
https://www.ncbi.nlm.nih.gov/pubmed/31399107
http://dx.doi.org/10.1186/s13023-019-1170-x
work_keys_str_mv AT rozasmfernanda associationbetweenphenotypeanddeletionsizein22q112microdeletionsyndromesystematicreviewandmetaanalysis
AT benavidesfelipe associationbetweenphenotypeanddeletionsizein22q112microdeletionsyndromesystematicreviewandmetaanalysis
AT leonluis associationbetweenphenotypeanddeletionsizein22q112microdeletionsyndromesystematicreviewandmetaanalysis
AT repettogabrielam associationbetweenphenotypeanddeletionsizein22q112microdeletionsyndromesystematicreviewandmetaanalysis