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
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