Identification of bi-allelic LFNG variants in three patients and further clinical and molecular refinement of spondylocostal dysostosis 3.
LFNG
exome sequencing
neonatal
notch signaling pathway
prenatal
respiratory distress
splicing
spondylocostal dysostosis
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
22
03
2023
received:
19
12
2022
accepted:
25
03
2023
medline:
5
7
2023
pubmed:
11
4
2023
entrez:
10
4
2023
Statut:
ppublish
Résumé
Spondylocostal dysostosis (SCD), a condition characterized by multiple segmentation defects of the vertebrae and rib malformations, is caused by bi-allelic variants in one of the genes involved in the Notch signaling pathway that tunes the "segmentation clock" of somitogenesis: DLL3, HES7, LFNG, MESP2, RIPPLY2, and TBX6. To date, seven individuals with LFNG variants have been reported in the literature. In this study we describe two newborns and one fetus with SCD, who were found by trio-based exome sequencing (trio-ES) to carry homozygous (c.822-5C>T) or compound heterozygous (c.[863dup];[1063G>A]) and (c.[521G>T];[890T>G]) variants in LFNG. Notably, the c.822-5C>T change, affecting the polypyrimidine tract of intron 5, is the first non-coding variant reported in LFNG. This study further refines the clinical and molecular features of spondylocostal dysostosis 3 and adds to the numerous investigations supporting the usefulness of trio-ES approach in prenatal and neonatal settings.
Substances chimiques
TBX6 protein, human
0
T-Box Domain Proteins
0
DLL3 protein, human
0
Membrane Proteins
0
Intracellular Signaling Peptides and Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
230-237Informations de copyright
© 2023 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
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