Comorbidity of congenital heart defects and holoprosencephaly is likely genetically driven and gene-specific.
Adolescent
Adult
Brain
/ metabolism
Cell Cycle Proteins
/ genetics
Child
Child, Preschool
Comorbidity
Eye Proteins
/ genetics
Female
Heart Defects, Congenital
/ genetics
Holoprosencephaly
/ genetics
Homeodomain Proteins
/ genetics
Humans
Infant
Infant, Newborn
Male
Middle Aged
Mutation
/ genetics
Nerve Tissue Proteins
/ genetics
Nuclear Proteins
/ genetics
Phenotype
Transcription Factors
/ genetics
Young Adult
Homeobox Protein SIX3
comorbidity
congenital heart disease
genomic sequencing
holoprosencephaly
Journal
American journal of medical genetics. Part C, Seminars in medical genetics
ISSN: 1552-4876
Titre abrégé: Am J Med Genet C Semin Med Genet
Pays: United States
ID NLM: 101235745
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
05
11
2019
revised:
23
01
2020
accepted:
24
01
2020
pubmed:
6
2
2020
medline:
7
1
2021
entrez:
6
2
2020
Statut:
ppublish
Résumé
Comorbidity of holoprosencephaly (HPE) and congenital heart disease (CHD) in individuals with genetic variants in known HPE-related genes has been recurrently observed. Morphogenesis of the brain and heart from very early stages are regulated by several biological pathways, some of them involved in both heart and brain development as evidenced by genetic studies on model organisms. For instance, downregulation of Hedgehog or Nodal signaling pathways, both known as major triggers of HPE, has been shown to play a role in the pathogenesis of CHD, including structural defects and left-right asymmetry defects. In this study, individuals with various types of HPE were investigated clinically and by genomic sequencing. Cardiac phenotypes were assessed in 434 individuals with HPE who underwent targeted sequencing. CHDs were identified in 8% (n = 33) of individuals, including 10 (30%) cases of complex heart disease. Only four individuals (4/33) had damaging variants in the known HPE genes STAG2, SIX3, and SHH. Interestingly, no CHD was identified in the 37 individuals of our cohort with pathogenic variants in ZIC2. These findings suggest that CHD occurs more frequently in HPE-affected individuals with or without identifiable genetic variants, and this co-occurrence may be genetically driven and gene-specific.
Identifiants
pubmed: 32022405
doi: 10.1002/ajmg.c.31770
doi:
Substances chimiques
Cell Cycle Proteins
0
Eye Proteins
0
Homeodomain Proteins
0
Nerve Tissue Proteins
0
Nuclear Proteins
0
STAG2 protein, human
0
Transcription Factors
0
ZIC2 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
154-158Subventions
Organisme : NHGRI NIH HHS
Pays : United States
Informations de copyright
© 2020 Wiley Periodicals, Inc.
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