Comorbidity of congenital heart defects and holoprosencephaly is likely genetically driven and gene-specific.

Autor:	Tekendo-Ngongang C; Medical Genetics Branch, National Human Genome Research Institutes, National Institutes of Health, Bethesda, Maryland., Owosela B; Medical Genetics Branch, National Human Genome Research Institutes, National Institutes of Health, Bethesda, Maryland., Muenke M; Medical Genetics Branch, National Human Genome Research Institutes, National Institutes of Health, Bethesda, Maryland., Kruszka P; Medical Genetics Branch, National Human Genome Research Institutes, National Institutes of Health, Bethesda, Maryland.
Jazyk:	angličtina
Zdroj:	American journal of medical genetics. Part C, Seminars in medical genetics [Am J Med Genet C Semin Med Genet] 2020 Mar; Vol. 184 (1), pp. 154-158. Date of Electronic Publication: 2020 Feb 05.
DOI:	10.1002/ajmg.c.31770
Abstrakt:	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. (© 2020 Wiley Periodicals, Inc.)
Databáze:	MEDLINE
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