Discovery of pathogenic variants in EFEMP2 and RAG1 and undetectable fetal phenotype: A challenge of prenatal exome sequencing.
Journal
Prenatal diagnosis
ISSN: 1097-0223
Titre abrégé: Prenat Diagn
Pays: England
ID NLM: 8106540
Informations de publication
Date de publication:
25 Jun 2024
25 Jun 2024
Historique:
revised:
09
06
2024
received:
06
11
2023
accepted:
11
06
2024
medline:
26
6
2024
pubmed:
26
6
2024
entrez:
26
6
2024
Statut:
aheadofprint
Résumé
Exome sequencing in prenatal context confronts with pathogenic variants associated with phenotypes that are not detectable prenatally. A consanguineous couple was referred at 24 weeks of gestation for prenatal genetic investigations after ultrasonography findings including decreased fetal movements, hypoplastic male external genitalia, retrognathia, prefrontal edema, anomalies of the great vessels with pulmonary atresia and dilated tortuous aorta. Prenatal trio exome sequencing identified two homozygous likely pathogenic variants, i.e. a missense in EFEMP2 involved in cutis laxa and a nonsense in RAG1 involved in several types of severe combined immunodeficiency. The fetal ultrasonographic phenotype was partially compatible with previously reported prenatal presentations secondary to EFEMP2 biallelic variants, but prenatal presentations have never been reported for RAG1 related disorders because the RAG1 phenotype is undetectable during pregnancy. Both EFEMP2 and RAG1 variants were disclosed to the couple because the EFEMP2 variant was considered causative for the fetal ultrasonographic phenotype and the RAG1 variant was considered a finding of strong interest for genetic counselling and monitoring of future pregnancies following the American College of Medical Genetics and Genomics recommendations about the discovery of incidental findings in fetal exome sequencing in prenatal diagnosis.
Sections du résumé
BACKGROUND
BACKGROUND
Exome sequencing in prenatal context confronts with pathogenic variants associated with phenotypes that are not detectable prenatally.
MATERIALS AND METHODS
METHODS
A consanguineous couple was referred at 24 weeks of gestation for prenatal genetic investigations after ultrasonography findings including decreased fetal movements, hypoplastic male external genitalia, retrognathia, prefrontal edema, anomalies of the great vessels with pulmonary atresia and dilated tortuous aorta.
RESULT
RESULTS
Prenatal trio exome sequencing identified two homozygous likely pathogenic variants, i.e. a missense in EFEMP2 involved in cutis laxa and a nonsense in RAG1 involved in several types of severe combined immunodeficiency.
DISCUSSION
CONCLUSIONS
The fetal ultrasonographic phenotype was partially compatible with previously reported prenatal presentations secondary to EFEMP2 biallelic variants, but prenatal presentations have never been reported for RAG1 related disorders because the RAG1 phenotype is undetectable during pregnancy.
CONCLUSION
CONCLUSIONS
Both EFEMP2 and RAG1 variants were disclosed to the couple because the EFEMP2 variant was considered causative for the fetal ultrasonographic phenotype and the RAG1 variant was considered a finding of strong interest for genetic counselling and monitoring of future pregnancies following the American College of Medical Genetics and Genomics recommendations about the discovery of incidental findings in fetal exome sequencing in prenatal diagnosis.
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 John Wiley & Sons Ltd.
Références
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Renard M, Holm T, Veith R, et al. Altered TGFbeta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin‐4 deficiency. Eur J Hum Genet. 2010;18(8):895‐901. Epub 2010 Apr 14. PMID: 20389311; PMCID: PMC2987390. https://doi.org/10.1038/ejhg.2010.45
Zhang X, Kang X, Yang M, et al. A variant of RAG1 gene identified in severe combined immunodeficiency: a case report. BMC Pediatr. 2023;23(1):56. PMID: 36732712; PMCID: PMC9896705. https://doi.org/10.1186/s12887‐022‐03822‐0
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