Genome Sequencing Identifies the Pathogenic Variant Missed by Prior Testing in an Infant with Marfan Syndrome

Monica H Wojcik; Katri Thiele; Carly F Grant; Katherine Chao; Julia Goodrich; Anne O'Donnell-Luria; Ronald V Lacro; Wen-Hann Tan; Pankaj B Agrawal

doi:10.1016/j.jpeds.2019.05.029

Genome Sequencing Identifies the Pathogenic Variant Missed by Prior Testing in an Infant with Marfan Syndrome

J Pediatr. 2019 Oct:213:235-240. doi: 10.1016/j.jpeds.2019.05.029. Epub 2019 Jun 22.

Authors

Monica H Wojcik¹, Katri Thiele², Carly F Grant³, Katherine Chao⁴, Julia Goodrich⁴, Anne O'Donnell-Luria⁵, Ronald V Lacro⁶, Wen-Hann Tan⁷, Pankaj B Agrawal⁸

Affiliations

¹ Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: [email protected].
² Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
³ Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital-Center for Cancer Risk Assessment, Boston, MA, USA.
⁴ The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁵ Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁶ Department of Cardiology, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
⁷ Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Abstract

We describe an infant with a phenotype typical of early onset Marfan syndrome whose genetic evaluation, including Sanger sequencing and deletion/duplication testing of FBN1 and exome sequencing, was negative. Ultimately, genome sequencing revealed a deletion missed on prior testing, demonstrating the unique utility of genome sequencing for molecular genetic diagnosis.

Keywords: FBN1; deletion; fibrillin; genetic.

Publication types

Case Reports
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Exome
Fatal Outcome
Fibrillin-1 / genetics*
Gene Deletion
Gene Dosage
Genetic Variation
Genome, Human
Humans
Infant
Male
Marfan Syndrome / diagnosis*
Marfan Syndrome / genetics*
Phenotype
Polymerase Chain Reaction
Sequence Analysis, DNA*

Substances

FBN1 protein, human
Fibrillin-1

Abstract

Publication types

MeSH terms

Substances

Grants and funding