Exome sequencing identifies de novo pathogenic variants in FBN1 and TRPS1 in a patient with a complex connective tissue phenotype.

Autor:	Zastrow DB; Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, California 94305, USA.; Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA., Zornio PA; Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, California 94305, USA.; Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA., Dries A; Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, California 94305, USA.; Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA., Kohler J; Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, California 94305, USA.; Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA., Fernandez L; Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, California 94305, USA.; Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA., Waggott D; Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, California 94305, USA.; Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA., Walkiewicz M; Baylor Miraca Genetics Laboratories, Houston, Texas 77021-2024, USA., Eng CM; Baylor Miraca Genetics Laboratories, Houston, Texas 77021-2024, USA., Manning MA; Department of Pathology, Stanford School of Medicine, Stanford, California 94305, USA.; Department of Pediatrics, Stanford School of Medicine, Stanford, California 94305, USA., Farrelly E; Lucille Packard Children's Hospital Stanford, Palo Alto, California 94304, USA., Fisher PG; Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, California 94305, USA.; Department of Pediatrics, Stanford School of Medicine, Stanford, California 94305, USA.; Department of Neurology, Stanford School of Medicine, Stanford, California 94304, USA., Ashley EA; Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, California 94305, USA.; Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA.; Department of Genetics, Stanford School of Medicine, Stanford, California 94305, USA., Bernstein JA; Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, California 94305, USA.; Department of Pediatrics, Stanford School of Medicine, Stanford, California 94305, USA.; Lucille Packard Children's Hospital Stanford, Palo Alto, California 94304, USA., Wheeler MT; Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, California 94305, USA.; Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA.
Jazyk:	angličtina
Zdroj:	Cold Spring Harbor molecular case studies [Cold Spring Harb Mol Case Stud] 2017 Jan; Vol. 3 (1), pp. a001388.
DOI:	10.1101/mcs.a001388
Abstrakt:	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:	MEDLINE
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