Cardiomyopathy due to PRDM16 mutation: First description of a fetal presentation, with possible modifier genes.
Adult
Cardiomyopathies
/ diagnosis
DNA-Binding Proteins
/ genetics
Female
Genes, Modifier
/ genetics
Genetic Heterogeneity
Genetic Predisposition to Disease
Heart Defects, Congenital
/ diagnosis
Humans
Infant, Newborn
Labor Presentation
Male
Middle Aged
Mutation
/ genetics
Pedigree
Pregnancy
Transcription Factors
/ genetics
Exome Sequencing
PRDM16
TTN
cardiomyopathy
exome sequencing
fetal pathology
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:
25
11
2019
accepted:
09
01
2020
pubmed:
23
1
2020
medline:
7
1
2021
entrez:
23
1
2020
Statut:
ppublish
Résumé
PRDM16 (positive regulatory domain 16) is localized in the critical region for cardiomyopathy in patients with deletions of chromosome 1p36, as defined by Gajecka et al., American Journal of Medical Genetics, 2010, 152A, 3074-3083, and encodes a zinc finger transcription factor. We present the first fetal case of left ventricular non-compaction (LVNC) with a PRDM16 variant. The third-trimester obstetric ultrasound revealed a hydropic fetus with hydramnios and expanded hypokinetic heart. After termination of pregnancy, foetopathology showed a eutrophic fetus with isolated cardiomegaly. Endocardial fibroelastosis was associated with non-compaction of the myocardium of the left ventricle. Exome sequencing (ES) identified a de novo unreported p.(Gln353*) heterozygous nonsense variant in PRDM16. ES also identified two rare variants of unknown significance, according to the American College of Medical Genetics and Genomics guidelines, in the titin gene (TTN): a de novo missense p.(Lys14773Asn) variant and a c.33043+5A>G variant inherited from the mother. Along with the PRDM16 de novo probably pathogenic variant, TTN VOUS variants could possibly contribute to the severity and early onset of the cardiac phenotype. Because of the genetic heterogeneity of cardiomyopathies, large panels or even ES could be considered as the main approaches for the molecular diagnosis, particularly in fetal presentations, where multiple hits seem to be common.
Identifiants
pubmed: 31965688
doi: 10.1002/ajmg.c.31766
doi:
Substances chimiques
DNA-Binding Proteins
0
PRDM16 protein, human
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
129-135Subventions
Organisme : Conseil régional de Bourgogne-Franche-Comté
ID : plan d'actions régional pour l'innovation (PARI)
Pays : International
Organisme : European Union
ID : PO FEDER-FSE Bourgogne 2014/2020 programs
Pays : International
Informations de copyright
© 2020 Wiley Periodicals, Inc.
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