Exome sequencing efficacy and phenotypic expansions involving esophageal atresia/tracheoesophageal fistula plus.
Fanconi anemia
NRXN1
TCF4
esophageal atresia
exome sequencing
tracheoesophageal fistula
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
01
09
2022
received:
22
08
2022
accepted:
05
09
2022
pubmed:
23
9
2022
medline:
15
11
2022
entrez:
22
9
2022
Statut:
ppublish
Résumé
Esophageal atresia/tracheoesophageal fistula (EA/TEF) is a life-threatening birth defect that often occurs with other major birth defects (EA/TEF+). Despite advances in genetic testing, a molecular diagnosis can only be made in a minority of EA/TEF+ cases. Here, we analyzed clinical exome sequencing data and data from the DECIPHER database to determine the efficacy of exome sequencing in cases of EA/TEF+ and to identify phenotypic expansions involving EA/TEF. Among 67 individuals with EA/TEF+ referred for clinical exome sequencing, a definitive or probable diagnosis was made in 11 cases for an efficacy rate of 16% (11/67). This efficacy rate is significantly lower than that reported for other major birth defects, suggesting that polygenic, multifactorial, epigenetic, and/or environmental factors may play a particularly important role in EA/TEF pathogenesis. Our cohort included individuals with pathogenic or likely pathogenic variants that affect TCF4 and its downstream target NRXN1, and FANCA, FANCB, and FANCC, which are associated with Fanconi anemia. These cases, previously published case reports, and comparisons to other EA/TEF genes made using a machine learning algorithm, provide evidence in support of a potential pathogenic role for these genes in the development of EA/TEF.
Identifiants
pubmed: 36135330
doi: 10.1002/ajmg.a.62976
pmc: PMC9669235
mid: NIHMS1835382
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3492-3504Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : R01 HD098458
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT098051
Pays : United Kingdom
Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
Reprod Toxicol. 1993 Sep-Oct;7(5):405-21
pubmed: 8274816
Mol Genet Genomic Med. 2018 Nov;6(6):1068-1078
pubmed: 30318729
Am J Med Genet A. 2005 Aug 15;137(1):55-8
pubmed: 16015582
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
J Pediatr Genet. 2018 Dec;7(4):164-173
pubmed: 30430034
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
J Pediatr Surg. 2003 Jun;38(6):852-6
pubmed: 12778380
Hum Mutat. 2015 May;36(5):562-8
pubmed: 25754594
Am J Med Genet A. 2011 Oct;155A(10):2370-80
pubmed: 21910217
Am J Med Genet A. 2011 Dec;155A(12):3071-4
pubmed: 22052692
Am J Hum Genet. 2009 Apr;84(4):524-33
pubmed: 19344873
J Med Genet. 2006 Sep;43(9):750-4
pubmed: 16679491
Eur J Hum Genet. 2012 Dec;20(12):1240-7
pubmed: 22617343
Genet Med. 2017 Jan;19(1):53-61
pubmed: 27195815
J Assist Reprod Genet. 2018 Jun;35(6):953-964
pubmed: 29855751
J Genet Couns. 2019 Apr;28(2):182-193
pubmed: 30648779
J Med Genet. 2006 Jul;43(7):545-54
pubmed: 16299066
Surgery. 2014 Aug;156(2):483-91
pubmed: 24947650
Fam Cancer. 2004;3(3-4):241-8
pubmed: 15516848
Am J Hum Genet. 2007 May;80(5):994-1001
pubmed: 17436255
Bioinformatics. 2014 Dec 1;30(23):3387-9
pubmed: 25123899
Am J Med Genet. 1997 Jan 10;68(1):86-90
pubmed: 8986283
Arch Dis Child. 1993 Jun;68(6):743-8
pubmed: 8333763
Hum Mutat. 2012 Dec;33(12):1676-86
pubmed: 22777675
Am J Med Genet A. 2013 Apr;161A(4):717-31
pubmed: 23495017
Am J Med Genet C Semin Med Genet. 2018 Dec;178(4):440-446
pubmed: 30580478
Nucleic Acids Res. 2011 Jan;39(Database issue):D842-8
pubmed: 21051359
Genet Med. 2016 Jul;18(7):696-704
pubmed: 26633542
Korean J Pediatr. 2010 Jun;53(6):705-10
pubmed: 21189942
Aust Paediatr J. 1978 Sep;14(3):182-4
pubmed: 728011
Eur J Med Genet. 2016 Oct;59(10):546-8
pubmed: 27614115
Semin Pediatr Surg. 2009 Feb;18(1):2-11
pubmed: 19103415
Clin Genet. 1992 Apr;41(4):169-74
pubmed: 1576752
PLoS Genet. 2013;9(9):e1003797
pubmed: 24086149
Am J Hum Genet. 2008 Jan;82(1):199-207
pubmed: 18179900
J Med Genet. 2022 Mar;59(3):270-278
pubmed: 33461977
Eur J Hum Genet. 2016 Dec;24(12):1715-1723
pubmed: 27436264
Mol Psychiatry. 2016 Jul;21(7):936-45
pubmed: 26370147
Hum Mutat. 2012 Jan;33(1):64-72
pubmed: 22045651
Birth Defects Res. 2017 Nov 1;109(18):1504-1514
pubmed: 29152924
Am J Hum Genet. 2009 Nov;85(5):655-66
pubmed: 19896112
Eur J Med Genet. 2010 Sep-Oct;53(5):333-6
pubmed: 20601258
Birth Defects Res A Clin Mol Teratol. 2016 Jul;106(7):542-8
pubmed: 26931365
Birth Defects Res. 2020 May 15;112(9):688-698
pubmed: 32319733
Am J Hum Genet. 2017 Jan 5;100(1):105-116
pubmed: 27939639
Eur J Hum Genet. 2014 Sep;22(9):1077-84
pubmed: 24398799
Nucleic Acids Res. 2014 Jan;42(Database issue):D986-92
pubmed: 24174537
Pediatrics. 1993 Jun;91(6):1116-20
pubmed: 8502512
JAMA Pediatr. 2017 Dec 4;171(12):e173438
pubmed: 28973083
Am J Hum Genet. 2008 Jan;82(1):150-9
pubmed: 18179893
Am J Hum Genet. 2007 May;80(5):988-93
pubmed: 17436254
Eur J Med Genet. 2007 May-Jun;50(3):163-75
pubmed: 17336605
Gene. 2018 Jun 30;661:182-188
pubmed: 29621589
Eur J Med Genet. 2014 Aug;57(8):440-52
pubmed: 24931924
Am J Med Genet A. 2011 Nov;155A(11):2826-31
pubmed: 21964664