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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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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 |
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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 |
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