Partial Jacobsen syndrome phenotype in a patient with a de novo frameshift mutation in the ETS1 transcription factor.

Abstract

Jacobsen syndrome (OMIM #147791) is a rare contiguous gene disorder caused by deletions in distal 11q. The clinical phenotype is variable and can include dysmorphic features, varying degrees of intellectual disability, behavioral problems including autism and attention deficit hyperactivity disorder, congenital heart defects, structural kidney defects, genitourinary problems, immunodeficiency, and a bleeding disorder due to impaired platelet production and function. Previous studies combining both human and animal systems have implicated several disease-causing genes in distal 11q that contribute to the Jacobsen syndrome phenotype. One gene, ETS1, has been implicated in causing congenital heart defects, structural kidney defects, and immunodeficiency. We performed a comprehensive phenotypic analysis on a patient with congenital heart disease previously found to have a de novo frameshift mutation in ETS1, resulting in the loss of the DNA-binding domain of the protein. Our results suggest that loss of Ets1 causes a "partial Jacobsen syndrome phenotype" including congenital heart disease, facial dysmorphism, intellectual disability, and attention deficit hyperactivity disorder.

• Authors: Eva Tootleman, Barbara Malamut, Natacha Akshoomoff, Sarah N Mattson, Hal M Hoffman, Marilyn C Jones, Beth Printz, Sergey A Shiryaev, Paul Grossfeld
• Journal: Cold Spring Harbor molecular case studies (Cold Spring Harb Mol Case Stud) Vol. 5 Issue 3 (06 2019) ISSN: 2373-2873 [Electronic] United States
• PMID: 31160359 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2019 Tootleman et al.; Published by Cold Spring Harbor Laboratory Press.

Chemical References

• ETS1 protein, human
• Proto-Oncogene Protein c-ets-1

Topics

• Frameshift Mutation
• Heart Defects, Congenital (diagnosis, genetics, pathology)
• Humans
• Infant, Newborn
• Jacobsen Distal 11q Deletion Syndrome (diagnosis, genetics, pathology)
• Male
• Phenotype
• Proto-Oncogene Protein c-ets-1 (genetics)
• Sequence Deletion