Exome sequencing identifies de novo pathogenic variants in FBN1 and TRPS1 in a patient with a complex connective tissue phenotype
Autor: | Daryl Waggott, Annika M. Dries, Jonathan A. Bernstein, Magdalena Walkiewicz, Euan A. Ashley, Matthew T. Wheeler, Diane B. Zastrow, Liliana Fernandez, Paul G. Fisher, Ellyn Farrelly, Jennefer N. Kohler, Patricia A. Zornio, Christine M. Eng, Melanie A. Manning |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
Research Report
0301 basic medicine Marfan syndrome musculoskeletal diseases congenital hereditary and neonatal diseases and abnormalities superior pectus carinatum hammertoe Medizin thoracic scoliosis Bioinformatics protruding ear congenital diaphragmatic hernia 03 medical and health sciences sparse lateral eyebrow 0302 clinical medicine smooth philtrum Medicine pes planus thin nail Exome sequencing Genetic testing long philtrum umbilical hernia medicine.diagnostic_test business.industry malar flattening Congenital diaphragmatic hernia General Medicine medicine.disease Hypotonia fourth toe clinodactyly 3. Good health Umbilical hernia joint laxity Inguinal hernia 030104 developmental biology inguinal hernia sparse anterior scalp hair medicine.symptom central hypotonia business Fibrillin 030217 neurology & neurosurgery thin upper lip vermilion |
Zdroj: | Cold Spring Harbor Molecular Case Studies |
Popis: | Here we describe a patient who presented with a history of congenital diaphragmatic hernia, inguinal hernia, and recurrent umbilical hernia. She also has joint laxity, hypotonia, and dysmorphic features. A unifying diagnosis was not identified based on her clinical phenotype. As part of her evaluation through the Undiagnosed Diseases Network, trio whole-exome sequencing was performed. Pathogenic variants in FBN1 and TRPS1 were identified as causing two distinct autosomal dominant conditions, each with de novo inheritance. Fibrillin 1 (FBN1) mutations are associated with Marfan syndrome and a spectrum of similar phenotypes. TRPS1 mutations are associated with trichorhinophalangeal syndrome types I and III. Features of both conditions are evident in the patient reported here. Discrepant features of the conditions (e.g., stature) and the young age of the patient may have made a clinical diagnosis more difficult in the absence of exome-wide genetic testing. |
Databáze: | OpenAIRE |
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