Automated reanalysis, a novel way to diagnose an ultra-rare condition: Fibronectin-1-related spondylometaphyseal dysplasia (SMD-FN1).
Journal
Clinical dysmorphology
ISSN: 1473-5717
Titre abrégé: Clin Dysmorphol
Pays: England
ID NLM: 9207893
Informations de publication
Date de publication:
01 Jul 2021
01 Jul 2021
Historique:
pubmed:
20
2
2021
medline:
24
11
2021
entrez:
19
2
2021
Statut:
ppublish
Résumé
We report a further case of spondylometaphyseal dysplasia - corner fracture type due to the fibronectin-1 gene (SMD-FN1) in a child originally thought to have metaphyseal chondrodysplasia-Brussels type (MCD Brussels). We highlight phenotypic differences with the SMD-FN1 published reports. This case is unique in terms of the method of molecular confirmation. Findings from the 100 000 Genomes Project were originally negative (in both tier 1 and 2); however, subsequent reanalysis, initiated by an automated search for new gene-disease associations in PanelApp, highlighted a candidate diagnostic variant. Our child had short stature, facial dysmorphism, spondylometaphyseal dysplasia and corner fractures and a heterozygous de novo missense variant in FN1 (c.675C>G p.(Cys225Trp), which was likely pathogenic. The variant matched the clinical and radiological features and a diagnosis of SMD-FN1 was confirmed. We explore the diagnostic journey of this patient, compare her findings with the previous 15 patients reported with SMD-FN1 and discuss the diagnostic utility of automated reanalysis. We consider differences and similarities between MCD Brussels and SMD-FN1, by reviewing literature on both conditions and assess whether they are in fact the same disorder.
Identifiants
pubmed: 33605604
doi: 10.1097/MCD.0000000000000369
pii: 00019605-202107000-00009
doi:
Substances chimiques
FN1 protein, human
0
Fibronectins
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
154-158Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Références
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