دورية أكاديمية
Exome sequencing in individuals with cardiovascular laterality defects identifies potential candidate genes.
| العنوان: | Exome sequencing in individuals with cardiovascular laterality defects identifies potential candidate genes. |
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| المؤلفون: | Breuer K; Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany.; Department of Pediatric Cardiology, Pediatric Heart Center, University Hospital of Bonn, Bonn, Germany., Riedhammer KM; Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.; Department of Nephrology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany., Müller N; Department of Pediatric Cardiology, Pediatric Heart Center, University Hospital of Bonn, Bonn, Germany., Schaidinger B; Department of Pediatric Cardiology, Pediatric Heart Center, University Hospital of Bonn, Bonn, Germany., Dombrowsky G; Department of Congenital Heart Disease and Pediatric Cardiology, University Hospital of Schleswig-Holstein, Kiel, Germany., Dittrich S; Department of Pediatric Cardiology, University of Erlangen-Nürnberg, Erlangen, Germany., Zeidler S; Pediatric Department, Asklepios clinics, Sankt Augustin, Germany., Bauer UMM; Competence Network for Congenital Heart Defects & National Register for Congenital Heart Defects, German Center for Cardiovascular Research (DZHK), Berlin, Germany., Westphal DS; Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Berlin, Germany.; Department of Internal Medicine I, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany., Meitinger T; Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany., Dakal TC; Department of Biotechnology, Mohanlal Sukhadia University Udaipur, Udaipur, Rajasthan, India., Hitz MP; Department of Congenital Heart Disease and Pediatric Cardiology, University Hospital of Schleswig-Holstein, Kiel, Germany.; DZHK (German Centre for Cardiovascular Research) Partner Site, Kiel, Germany., Breuer J; Department of Pediatric Cardiology, Pediatric Heart Center, University Hospital of Bonn, Bonn, Germany., Reutter H; Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany.; Division of Neonatology and Pediatric Intensive Care Medicine, Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany., Hilger AC; Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany., Hoefele J; Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany. julia.hoefele@tum.de. |
| المصدر: | European journal of human genetics : EJHG [Eur J Hum Genet] 2022 Aug; Vol. 30 (8), pp. 946-954. Date of Electronic Publication: 2022 Apr 26. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9302235 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5438 (Electronic) Linking ISSN: 10184813 NLM ISO Abbreviation: Eur J Hum Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2003->: London : Nature Publishing Group Original Publication: Basel ; New York : Karger, [1992- |
| مواضيع طبية MeSH: | Heart Defects, Congenital*/genetics , Heterotaxy Syndrome*/genetics , Situs Inversus*/genetics, Exome ; Humans ; Membrane Proteins/genetics ; Nucleocytoplasmic Transport Proteins/genetics ; Phenotype ; Exome Sequencing |
| مستخلص: | The birth prevalence of laterality defects is about 1.1/10,000 comprising different phenotypes ranging from situs inversus totalis to heterotaxy, mostly associated with complex congenital heart defects (CHD) and situs abnormalities such as intestinal malrotation, biliary atresia, asplenia, or polysplenia. A proportion of laterality defects arise in the context of primary ciliary dyskinesia (PCD) accompanied by respiratory symptoms or infertility. In this study, exome sequencing (ES) was performed in 14 case-parent trios/quattros with clinical exclusion of PCD prior to analysis. Moreover, all cases and parents underwent detailed clinical phenotyping including physical examination, echocardiography by a skilled paediatric cardiologist and abdominal ultrasound examinations not to miss mildly affected individuals. Subsequent survey of the exome data comprised filtering for monoallelic de novo, rare biallelic, and X-linked recessive variants. In two families, rare variants of uncertain significance (VUS) in PKD1L1 and ZIC3 were identified. Both genes have been associated with laterality defects. In two of the remaining families, biallelic variants in LMBRD1 and DNAH17, respectively, were prioritized. In another family, an ultra-rare de novo variant in WDR47 was found. Extensive exome survey of 2,109 single exomes of individuals with situs inversus totalis, heterotaxy, or isolated CHD identified two individuals with novel monoallelic variants in WDR47, but no further individuals with biallelic variants in DNAH17 or LMBRD1. Overall, ES of 14 case-parent trios/quattros with cardiovascular laterality defects identified rare VUS in two families in known disease-associated genes PKD1L1 and ZIC3 and suggests DNAH17, LMBRD1, and WDR47 as potential genes involved in laterality defects. (© 2022. The Author(s).) |
| References: | Lin AE, Krikov S, Riehle-Colarusso T, Frias JL, Belmont J, Anderka M, et al. Laterality defects in the national birth defects prevention study (1998–2007): Birth prevalence and descriptive epidemiology. Am J Med Genet A. 2014;164A:2581–91. (PMID: 10.1002/ajmg.a.36695) McGovern E, Kelleher E, Potts JE, O’Brien J, Walsh K, Nolke L, et al. Predictors of poor outcome among children with heterotaxy syndrome: A retrospective review. Open Heart. 2016;3:e000328. (PMID: 10.1136/openhrt-2015-000328) Li AH, Hanchard NA, Azamian M, D’Alessandro LCA, Coban-Akdemir Z, Lopez KN, et al. Genetic architecture of laterality defects revealed by whole exome sequencing. Eur J Hum Genet. 2019;27:563–73. (PMID: 10.1038/s41431-018-0307-z) Versacci P, Pugnaloni F, Digilio MC, Putotto C, Unolt M, Calcagni G, et al. Some isolated cardiac malformations can be related to laterality defects. J Cardiovasc Dev Dis. 2018;5:24. (PMID: 10.3390/jcdd5020024) Kosaki K, Casey B. Genetics of human left-right axis malformations. Semin Cell Dev Biol. 1998;9:89–99. (PMID: 10.1006/scdb.1997.0187) Belmont JW, Mohapatra B, Towbin JA, Ware SM. Molecular genetics of heterotaxy syndromes. Curr Opin Cardiol. 2004;19:216–20. (PMID: 10.1097/00001573-200405000-00005) Kremer LS, Bader DM, Mertes C, Kopajtich R, Pichler G, Iuso A, et al. Genetic diagnosis of Mendelian disorders via RNA sequencing. Nat Commun. 2017;8:15824. (PMID: 10.1038/ncomms15824) Plagnol V, Curtis J, Epstein M, Mok KY, Stebbings E, Grigoriadou S, et al. A robust model for read count data in exome sequencing experiments and implications for copy number variant calling. Bioinformatics 2012;28:2747–54. (PMID: 10.1093/bioinformatics/bts526) Ellard S, Baple EL, Berry I, Forrester N, Turnbull C, Owens M, et al. ACGS Best Practice Guidelines for Variant Classification 2019. https://www.acgsukcom/media/11285/uk-practice-guidelines-for-variant-classification-2019-v1-0-3pdf . 2019. Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020;22:245–57. (PMID: 10.1038/s41436-019-0686-8) Abou Tayoun AN, Pesaran T, DiStefano MT, Oza A, Rehm HL, Biesecker LG, et al. Recommendations for interpreting the loss of function PVS1 ACMG/AMP variant criterion. Hum Mutat. 2018;39:1517–24. (PMID: 10.1002/humu.23626) Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24. (PMID: 10.1038/gim.2015.30) Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alfoldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 2020;581:434–43. (PMID: 10.1038/s41586-020-2308-7) Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 2016;536:285–91. (PMID: 10.1038/nature19057) Sifrim A, Hitz MP, Wilsdon A, Breckpot J, Turki SH, Thienpont B, et al. Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing. Nat Genet. 2016;48:1060–5. (PMID: 10.1038/ng.3627) Kitaguchi T, Nagai T, Nakata K, Aruga J, Mikoshiba K. Zic3 is involved in the left-right specification of the Xenopus embryo. Development 2000;127:4787–95. (PMID: 10.1242/dev.127.22.4787) Rutsch F, Gailus S, Miousse IR, Suormala T, Sagne C, Toliat MR, et al. Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism. Nat Genet. 2009;41:234–9. (PMID: 10.1038/ng.294) Oladipo O, Rosenblatt DS, Watkins D, Miousse IR, Sprietsma L, Dietzen DJ, et al. Cobalamin F disease detected by newborn screening and follow-up on a 14-year-old patient. Pediatrics 2011;128:e1636–40. (PMID: 10.1542/peds.2010-3518) Deciphering Developmental Disorders Study G, Constantinou P, D’Alessandro M, Lochhead P, Samant S, Bisset WM, et al. A new, atypical case of cobalamin f disorder diagnosed by whole exome sequencing. Mol Syndromol. 2016;6:254–8. Imtiaz F, Allam R, Ramzan K, Al-Sayed M. Variation in DNAH1 may contribute to primary ciliary dyskinesia. BMC Med Genet. 2015;16:14. (PMID: 10.1186/s12881-015-0162-5) Loges NT, Antony D, Maver A, Deardorff MA, Gulec EY, Gezdirici A, et al. Recessive DNAH9 loss-of-function mutations cause laterality defects and subtle respiratory ciliary-beating defects. Am J Hum Genet. 2018;103:995–1008. (PMID: 10.1016/j.ajhg.2018.10.020) Omran H, Haffner K, Volkel A, Kuehr J, Ketelsen UP, Ross UH, et al. Homozygosity mapping of a gene locus for primary ciliary dyskinesia on chromosome 5p and identification of the heavy dynein chain DNAH5 as a candidate gene. Am J Respir Cell Mol Biol. 2000;23:696–702. (PMID: 10.1165/ajrcmb.23.5.4257) Bartoloni L, Blouin JL, Pan Y, Gehrig C, Maiti AK, Scamuffa N, et al. Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia. Proc Natl Acad Sci USA. 2002;99:10282–6. (PMID: 10.1073/pnas.152337699) Vetrini F, D’Alessandro LC, Akdemir ZC, Braxton A, Azamian MS, Eldomery MK, et al. Bi-allelic mutations in PKD1L1 are associated with laterality defects in humans. Am J Hum Genet. 2016;99:886–93. (PMID: 10.1016/j.ajhg.2016.07.011) Le Fevre A, Baptista J, Ellard S, Overton T, Oliver A, Gradhand E, et al. Compound heterozygous Pkd1l1 variants in a family with two fetuses affected by heterotaxy and complex Chd. Eur J Med Genet. 2020;63:103657. (PMID: 10.1016/j.ejmg.2019.04.014) Grimes DT, Keynton JL, Buenavista MT, Jin X, Patel SH, Kyosuke S, et al. Genetic analysis reveals a hierarchy of interactions between polycystin-encoding genes and genes controlling cilia function during left-right determination. PLoS Genet. 2016;12:e1006070. (PMID: 10.1371/journal.pgen.1006070) Field S, Riley KL, Grimes DT, Hilton H, Simon M, Powles-Glover N, et al. Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2. Development 2011;138:1131–42. (PMID: 10.1242/dev.058149) Ware SM, Peng J, Zhu L, Fernbach S, Colicos S, Casey B, et al. Identification and functional analysis of ZIC3 mutations in heterotaxy and related congenital heart defects. Am J Hum Genet. 2004;74:93–105. (PMID: 10.1086/380998) Wessels MW, Kuchinka B, Heydanus R, Smit BJ, Dooijes D, de Krijger RR, et al. Polyalanine expansion in the ZIC3 gene leading to X-linked heterotaxy with VACTERL association: a new polyalanine disorder? J Med Genet. 2010;47:351–5. (PMID: 10.1136/jmg.2008.060913) Chung B, Shaffer LG, Keating S, Johnson J, Casey B, Chitayat D. From VACTERL-H to heterotaxy: Variable expressivity of ZIC3-related disorders. Am J Med Genet A. 2011;155A:1123–8. (PMID: 10.1002/ajmg.a.33859) Hilger AC, Halbritter J, Pennimpede T, van der Ven A, Sarma G, Braun DA, et al. Targeted resequencing of 29 candidate genes and mouse expression studies implicate ZIC3 and FOXF1 in human VATER/VACTERL association. Hum Mutat. 2015;36:1150–4. (PMID: 10.1002/humu.22859) Rosenblatt DS, Hosack A, Matiaszuk NV, Cooper BA, Laframboise R. Defect in vitamin B12 release from lysosomes: newly described inborn error of vitamin B12 metabolism. Science 1985;228:1319–21. (PMID: 10.1126/science.4001945) Vassiliadis A, Rosenblatt DS, Cooper BA, Bergeron JJ. Lysosomal cobalamin accumulation in fibroblasts from a patient with an inborn error of cobalamin metabolism (cblF complementation group): Visualization by electron microscope radioautography. Exp Cell Res. 1991;195:295–302. (PMID: 10.1016/0014-4827(91)90376-6) Buers I, Pennekamp P, Nitschke Y, Lowe C, Skryabin BV, Rutsch F. Lmbrd1 expression is essential for the initiation of gastrulation. J Cell Mol Med. 2016;20:1523–33. (PMID: 10.1111/jcmm.12844) Whitfield M, Thomas L, Bequignon E, Schmitt A, Stouvenel L, Montantin G, et al. Mutations in DNAH17, encoding a sperm-specific axonemal outer dynein arm heavy chain, cause isolated male infertility due to Asthenozoospermia. Am J Hum Genet. 2019;105:198–212. (PMID: 10.1016/j.ajhg.2019.04.015) Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Proteomics. Tissue-based map of the human proteome. Science 2015;347:1260419. (PMID: 10.1126/science.1260419) Wang W, Lundin VF, Millan I, Zeng A, Chen X, Yang J, et al. Nemitin, a novel Map8/Map1s interacting protein with Wd40 repeats. PLoS One. 2012;7:e33094. (PMID: 10.1371/journal.pone.0033094) Kannan M, Bayam E, Wagner C, Rinaldi B, Kretz PF, Tilly P, et al. WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy. Proc Natl Acad Sci USA. 2017;114:E9308–17. (PMID: 10.1073/pnas.1713625114) Chen Y, Zheng J, Li X, Zhu L, Shao Z, Yan X, et al. Wdr47 controls neuronal polarization through the camsap family microtubule minus-end-binding proteins. Cell Rep. 2020;31:107526. (PMID: 10.1016/j.celrep.2020.107526) Ta-Shma A, Perles Z, Yaacov B, Werner M, Frumkin A, Rein AJ, et al. A human laterality disorder associated with a homozygous WDR16 deletion. Eur J Hum Genet. 2015;23:1262–5. (PMID: 10.1038/ejhg.2014.265) MacArthur DG, Manolio TA, Dimmock DP, Rehm HL, Shendure J, Abecasis GR, et al. Guidelines for investigating causality of sequence variants in human disease. Nature 2014;508:469–76. (PMID: 10.1038/nature13127) |
| المشرفين على المادة: | 0 (LMBRD1 protein, human) 0 (Membrane Proteins) 0 (Nucleocytoplasmic Transport Proteins) 0 (PKD1L1 protein, human) |
| تواريخ الأحداث: | Date Created: 20220427 Date Completed: 20220805 Latest Revision: 20221207 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC9349204 |
| DOI: | 10.1038/s41431-022-01100-2 |
| PMID: | 35474353 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1476-5438 |
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| DOI: | 10.1038/s41431-022-01100-2 |