Exploring copy number variants in deceased fetuses and neonates with abnormal vertebral patterns and cervical ribs.
SNP arrays
cervical ribs
congenital anomalies
copy number variations
vertebral pattern
Journal
Birth defects research
ISSN: 2472-1727
Titre abrégé: Birth Defects Res
Pays: United States
ID NLM: 101701004
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
20
02
2020
revised:
03
07
2020
accepted:
21
07
2020
pubmed:
6
8
2020
medline:
19
8
2021
entrez:
6
8
2020
Statut:
ppublish
Résumé
Cervical patterning abnormalities are rare in the general population, but one variant, cervical ribs, is particularly common in deceased fetuses and neonates. The discrepancy between the incidence in the general population and early mortality is likely due to indirect selection against cervical ribs. The cause for the co-occurrence of cervical ribs and adverse outcome remains unidentified. Copy number variations resulting in gain or loss of specific genes involved in development and patterning could play a causative role. Radiographs of 374 deceased fetuses and infants, including terminations of pregnancies, stillbirths and neonatal deaths, were assessed. Copy number profiles of 265 patients were determined using single nucleotide polymorphism array. 274/374 patients (73.3%) had an abnormal vertebral pattern, which was associated with congenital abnormalities. Cervical ribs were present in 188/374 (50.3%) and were more common in stillbirths (69/128 [53.9%]) and terminations of pregnancies (101/188 [53.7%]), compared to live births (18/58, 31.0%). Large (likely) deleterious copy number variants and aneuploidies were prevalent in these patients. None of the rare copy number variants were recurrent or overlapped with candidate genes for vertebral patterning. The large variety of copy number variants in deceased fetuses and neonates with similar abnormalities of the vertebral pattern probably reflects the etiological heterogeneity of vertebral patterning abnormalities. This genetic heterogeneity corresponds with the hypothesis that cervical ribs can be regarded as a sign of disruption of critical, highly interactive stages of embryogenesis. The vertebral pattern can probably provide valuable information regarding fetal and neonatal outcome.
Sections du résumé
BACKGROUND
Cervical patterning abnormalities are rare in the general population, but one variant, cervical ribs, is particularly common in deceased fetuses and neonates. The discrepancy between the incidence in the general population and early mortality is likely due to indirect selection against cervical ribs. The cause for the co-occurrence of cervical ribs and adverse outcome remains unidentified. Copy number variations resulting in gain or loss of specific genes involved in development and patterning could play a causative role.
METHODS
Radiographs of 374 deceased fetuses and infants, including terminations of pregnancies, stillbirths and neonatal deaths, were assessed. Copy number profiles of 265 patients were determined using single nucleotide polymorphism array.
RESULTS
274/374 patients (73.3%) had an abnormal vertebral pattern, which was associated with congenital abnormalities. Cervical ribs were present in 188/374 (50.3%) and were more common in stillbirths (69/128 [53.9%]) and terminations of pregnancies (101/188 [53.7%]), compared to live births (18/58, 31.0%). Large (likely) deleterious copy number variants and aneuploidies were prevalent in these patients. None of the rare copy number variants were recurrent or overlapped with candidate genes for vertebral patterning.
CONCLUSIONS
The large variety of copy number variants in deceased fetuses and neonates with similar abnormalities of the vertebral pattern probably reflects the etiological heterogeneity of vertebral patterning abnormalities. This genetic heterogeneity corresponds with the hypothesis that cervical ribs can be regarded as a sign of disruption of critical, highly interactive stages of embryogenesis. The vertebral pattern can probably provide valuable information regarding fetal and neonatal outcome.
Identifiants
pubmed: 32755042
doi: 10.1002/bdr2.1786
pmc: PMC7689732
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1513-1525Informations de copyright
© 2020 The Authors. Birth Defects Research published by Wiley Periodicals LLC.
Références
Dev Biol. 1998 Mar 1;195(1):1-15
pubmed: 9520319
Clin Anat. 2009 Apr;22(3):331-6
pubmed: 19280652
Evodevo. 2011 May 06;2:11
pubmed: 21548920
Cancers (Basel). 2019 Apr 12;11(4):
pubmed: 31013831
Eur J Pediatr. 1992 Jun;151(6):432-4
pubmed: 1628671
Pediatr Dev Pathol. 2011 Nov-Dec;14(6):431-7
pubmed: 21711209
Ulster Med J. 2006 Jan;75(1):23-31
pubmed: 16457401
Dev Dyn. 2014 Jan;243(1):24-36
pubmed: 23813547
Ann Vasc Surg. 2014 May;28(4):924-32
pubmed: 24316293
Teratology. 1979 Apr;19(2):137-42
pubmed: 473066
J Med Genet. 2016 Jul;53(7):431-7
pubmed: 27084730
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12644-8
pubmed: 7809093
Pediatr Res. 2020 Mar;87(4):773-778
pubmed: 31645054
Obstet Gynecol. 2010 Aug;116(2 Pt 1):254-60
pubmed: 20664383
Obstet Gynecol Surv. 2016 Dec;71(12):741-750
pubmed: 28005137
Spine (Phila Pa 1976). 2007 Apr 15;32(8):904-10
pubmed: 17426637
J Exp Zool. 2001 Aug 15;291(2):195-204
pubmed: 11479918
Birth Defects Res. 2020 Nov;112(18):1513-1525
pubmed: 32755042
World Neurosurg. 2018 Feb;110:e965-e978
pubmed: 29203316
Am J Med Genet A. 2015 Nov;167A(11):2589-93
pubmed: 26174333
BMJ Case Rep. 2018 Dec 18;11(1):
pubmed: 30567892
J Ultrasound Med. 2008 Sep;27(9):1263-71
pubmed: 18716135
Lancet. 2011 Apr 23;377(9775):1448-63
pubmed: 21496911
Evolution. 2006 Dec;60(12):2643-54
pubmed: 17263123
N Engl J Med. 2012 Dec 6;367(23):2175-84
pubmed: 23215555
J Exp Zool B Mol Dev Evol. 2005 Mar 15;304(2):91-106
pubmed: 15660398
Int J Dent. 2010;2010:295728
pubmed: 20628592
Am J Med Genet A. 2004 Jul 15;128A(2):127-31
pubmed: 15214001
Mol Syndromol. 2013 Feb;4(1-2):94-105
pubmed: 23653580
Nat Genet. 2011 Aug 14;43(9):838-46
pubmed: 21841781
J Matern Fetal Neonatal Med. 2019 Jul;32(14):2280-2286
pubmed: 29353507
Eur J Med Genet. 2005 Apr-Jun;48(2):113-29
pubmed: 16053903
Evol Biol. 2012 Dec;39(4):456-471
pubmed: 23226903
Eur J Hum Genet. 2016 Dec;24(12):1715-1723
pubmed: 27436264
Ultrasound Obstet Gynecol. 2016 Mar;47(3):383-4
pubmed: 26511656
Br J Cancer. 2011 Oct 25;105(9):1392-5
pubmed: 21915120
Am J Med Genet A. 2012 Dec;158A(12):3087-100
pubmed: 23165726
Mol Genet Metab. 2014 Jan;111(1):4-15
pubmed: 24239177
J Exp Zool. 1999 Apr 15;285(1):19-26
pubmed: 10327647
J Anat. 2011 Sep;219(3):403-9
pubmed: 21689099
Cancers (Basel). 2019 Apr 10;11(4):
pubmed: 30974862
Ultrasound Obstet Gynecol. 2008 Sep;32(4):506-9
pubmed: 18537105
Dev Biol. 2010 Aug 1;344(1):7-15
pubmed: 20435029
Teratology. 1989 Feb;39(2):127-35
pubmed: 2784595
Ultrasound Obstet Gynecol. 2014 Feb;43(2):139-46
pubmed: 23897843
Genes Dev. 2002 Jun 1;16(11):1423-32
pubmed: 12050119
Nat Genet. 2014 Oct;46(10):1063-71
pubmed: 25217958
Ultrasound Obstet Gynecol. 2006 Jun;27(6):714-5
pubmed: 16628597
Clin Radiol. 1978 Jul;29(4):427-30
pubmed: 679617
Biometrics. 1977 Mar;33(1):159-74
pubmed: 843571
Cleft Palate Craniofac J. 2006 Sep;43(5):513-8
pubmed: 16986980
Lancet. 2007 Nov 17;370(9600):1715-25
pubmed: 18022035
Am J Med Genet. 1985 May;21(1):1-11
pubmed: 4003434
J Anat. 2015 Nov;227(5):673-85
pubmed: 26467243
Teratology. 1980 Jun;21(3):349-56
pubmed: 7455924