Automated reanalysis, a novel way to diagnose an ultra-rare condition: Fibronectin-1-related spondylometaphyseal dysplasia (SMD-FN1)
| Autor: | Ataf H. Sabir, Joo Wook Ahn, Jessica Man, Nana Ekuntan Mensah, Moira Cheung, Melita Irving, Juhi Singhal |
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| Rok vydání: | 2021 |
| Předmět: |
Pediatrics
medicine.medical_specialty Heterozygote Mutation Missense Osteochondrodysplasias Short stature Pathology and Forensic Medicine Facial dysmorphism medicine Missense mutation Humans Child Genetics (clinical) Fracture type Likely pathogenic Growth Disorders business.industry General Medicine Fibronectins Tibial Fractures Phenotype Spondylometaphyseal dysplasia Pediatrics Perinatology and Child Health Female Hip Joint Anatomy medicine.symptom business |
| Zdroj: | Clinical dysmorphology. 30(3) |
| ISSN: | 1473-5717 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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