Cargando…

Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation

BACKGROUND: Intestinal malrotation is a potentially life‐threatening congenital anomaly due to the risk of developing midgut volvulus. The reported incidence is 0.2%–1% and both apparently hereditary and sporadic cases have been reported. Intestinal malrotation is associated with a few syndromes wit...

Descripción completa

Detalles Bibliográficos
Autores principales: Salehi Karlslätt, Karin, Pettersson, Maria, Jäntti, Nina, Szafranski, Przemyslaw, Wester, Tomas, Husberg, Britt, Ullberg, Ulla, Stankiewicz, Pawel, Nordgren, Ann, Lundin, Johanna, Lindstrand, Anna, Nordenskjöld, Agneta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418355/
https://www.ncbi.nlm.nih.gov/pubmed/30632303
http://dx.doi.org/10.1002/mgg3.549
_version_ 1783403722163879936
author Salehi Karlslätt, Karin
Pettersson, Maria
Jäntti, Nina
Szafranski, Przemyslaw
Wester, Tomas
Husberg, Britt
Ullberg, Ulla
Stankiewicz, Pawel
Nordgren, Ann
Lundin, Johanna
Lindstrand, Anna
Nordenskjöld, Agneta
author_facet Salehi Karlslätt, Karin
Pettersson, Maria
Jäntti, Nina
Szafranski, Przemyslaw
Wester, Tomas
Husberg, Britt
Ullberg, Ulla
Stankiewicz, Pawel
Nordgren, Ann
Lundin, Johanna
Lindstrand, Anna
Nordenskjöld, Agneta
author_sort Salehi Karlslätt, Karin
collection PubMed
description BACKGROUND: Intestinal malrotation is a potentially life‐threatening congenital anomaly due to the risk of developing midgut volvulus. The reported incidence is 0.2%–1% and both apparently hereditary and sporadic cases have been reported. Intestinal malrotation is associated with a few syndromes with known genotype but the genetic contribution in isolated intestinal malrotation has not yet been reported. Rare copy number variants (CNVs) have been implicated in many congenital anomalies, and hence we sought to investigate the potential contribution of rare CNVs in intestinal malrotation. METHODS: Analysis of array comparative genomic hybridization (aCGH) data from 47 patients with symptomatic intestinal malrotation was performed. RESULTS: We identified six rare CNVs in five patients. Five CNVs involved syndrome loci: 7q11.23 microduplication, 16p13.11 microduplication, 18q terminal deletion, HDAC8 (Cornelia de Lange syndrome type 5 and FOXF1) as well as one intragenic deletion in GALNT14, not previously implicated in human disease. CONCLUSION: In the present study, we identified rare CNVs contributing pathogenic or potentially pathogenic alleles in five patients with syndromic intestinal malrotation, suggesting that CNV screening is indicated in intestinal malrotation with associated malformations or neurological involvements. In addition, we identified intestinal malrotation in two known syndromes (Cornelia de Lange type 5 and 18q terminal deletion syndrome) that has not previously been associated with gastrointestinal malformations.
format Online
Article
Text
id pubmed-6418355
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-64183552019-03-27 Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation Salehi Karlslätt, Karin Pettersson, Maria Jäntti, Nina Szafranski, Przemyslaw Wester, Tomas Husberg, Britt Ullberg, Ulla Stankiewicz, Pawel Nordgren, Ann Lundin, Johanna Lindstrand, Anna Nordenskjöld, Agneta Mol Genet Genomic Med Original Articles BACKGROUND: Intestinal malrotation is a potentially life‐threatening congenital anomaly due to the risk of developing midgut volvulus. The reported incidence is 0.2%–1% and both apparently hereditary and sporadic cases have been reported. Intestinal malrotation is associated with a few syndromes with known genotype but the genetic contribution in isolated intestinal malrotation has not yet been reported. Rare copy number variants (CNVs) have been implicated in many congenital anomalies, and hence we sought to investigate the potential contribution of rare CNVs in intestinal malrotation. METHODS: Analysis of array comparative genomic hybridization (aCGH) data from 47 patients with symptomatic intestinal malrotation was performed. RESULTS: We identified six rare CNVs in five patients. Five CNVs involved syndrome loci: 7q11.23 microduplication, 16p13.11 microduplication, 18q terminal deletion, HDAC8 (Cornelia de Lange syndrome type 5 and FOXF1) as well as one intragenic deletion in GALNT14, not previously implicated in human disease. CONCLUSION: In the present study, we identified rare CNVs contributing pathogenic or potentially pathogenic alleles in five patients with syndromic intestinal malrotation, suggesting that CNV screening is indicated in intestinal malrotation with associated malformations or neurological involvements. In addition, we identified intestinal malrotation in two known syndromes (Cornelia de Lange type 5 and 18q terminal deletion syndrome) that has not previously been associated with gastrointestinal malformations. John Wiley and Sons Inc. 2019-01-10 /pmc/articles/PMC6418355/ /pubmed/30632303 http://dx.doi.org/10.1002/mgg3.549 Text en © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Salehi Karlslätt, Karin
Pettersson, Maria
Jäntti, Nina
Szafranski, Przemyslaw
Wester, Tomas
Husberg, Britt
Ullberg, Ulla
Stankiewicz, Pawel
Nordgren, Ann
Lundin, Johanna
Lindstrand, Anna
Nordenskjöld, Agneta
Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation
title Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation
title_full Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation
title_fullStr Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation
title_full_unstemmed Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation
title_short Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation
title_sort rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418355/
https://www.ncbi.nlm.nih.gov/pubmed/30632303
http://dx.doi.org/10.1002/mgg3.549
work_keys_str_mv AT salehikarlslattkarin rarecopynumbervariantscontributepathogenicallelesinpatientswithintestinalmalrotation
AT petterssonmaria rarecopynumbervariantscontributepathogenicallelesinpatientswithintestinalmalrotation
AT janttinina rarecopynumbervariantscontributepathogenicallelesinpatientswithintestinalmalrotation
AT szafranskiprzemyslaw rarecopynumbervariantscontributepathogenicallelesinpatientswithintestinalmalrotation
AT westertomas rarecopynumbervariantscontributepathogenicallelesinpatientswithintestinalmalrotation
AT husbergbritt rarecopynumbervariantscontributepathogenicallelesinpatientswithintestinalmalrotation
AT ullbergulla rarecopynumbervariantscontributepathogenicallelesinpatientswithintestinalmalrotation
AT stankiewiczpawel rarecopynumbervariantscontributepathogenicallelesinpatientswithintestinalmalrotation
AT nordgrenann rarecopynumbervariantscontributepathogenicallelesinpatientswithintestinalmalrotation
AT lundinjohanna rarecopynumbervariantscontributepathogenicallelesinpatientswithintestinalmalrotation
AT lindstrandanna rarecopynumbervariantscontributepathogenicallelesinpatientswithintestinalmalrotation
AT nordenskjoldagneta rarecopynumbervariantscontributepathogenicallelesinpatientswithintestinalmalrotation