Trio-whole-exome sequencing and preimplantation genetic diagnosis for unexplained recurrent fetal malformations.
Adult
Alleles
Congenital Abnormalities
/ diagnosis
DNA Mutational Analysis
Female
Fetus
/ abnormalities
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Gestational Age
Humans
Male
Mutation
Phenotype
Pregnancy
Preimplantation Diagnosis
/ methods
Ultrasonography, Prenatal
Exome Sequencing
/ methods
Young Adult
Trio-whole-exome sequencing
nonconsanguineous family
preimplantation genetic diagnosis
unexplained recurrent fetal malformations
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
09
05
2019
revised:
19
09
2019
accepted:
16
10
2019
pubmed:
5
11
2019
medline:
23
7
2021
entrez:
5
11
2019
Statut:
ppublish
Résumé
Whole-exome sequencing (WES) is widely used to detect genetic mutations that cause Mendelian diseases, and has been successfully applied in combination with preimplantation genetic diagnosis (PGD) to avoid the transmission of genetic defects. We investigated 40 nonconsanguineous families with unexplained, recurrent fetal malformations (two or more malformed fetuses) from May 2016 to December 2018. Using Trio-WES, we identified 32 disease-associated variants in 40 families (80% positive rate), which were subsequently verified. Known Mendelian diseases were identified in 12 families (30%), highly suspected Mendelian diseases in 12 families (30%), variants with uncertain significance in 8 families (20%), and no noticeable variants for 8 families (20%). Further analysis showed variants in 22 genes may cause fetal malformations. Four gene variants were detected in fetuses for the first time, which expanded the spectrum of the disease phenotype. Two novel candidate genes may be related to fetal malformations. Of 26 couples receiving PGD on disease-associated genes, 3 healthy newborns were delivered, and 4 couples are undergoing pregnancies. We reported the fetal data and developed an optimized genetic testing strategy. Our finding strongly suggests the presence of single gene Mendelian disorders in 60% of those families, and PGD services for couples to have healthy babies.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
432-448Informations de copyright
© 2019 Wiley Periodicals, Inc.
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