Whole-exome analysis of foetal autopsy tissue reveals a frameshift mutation in OBSL1, consistent with a diagnosis of 3-M Syndrome

Christian R. Marshall, Sandra A. Farrell, Donna Cushing, Tara Paton, Tracy L. Stockley, Dimitri J. Stavropoulos, Peter N. Ray, Michael Szego, Lynette Lau, Sergio L. Pereira, Ronald D. Cohn, Richard F. Wintle, Adel M. Abuzenadah, Muhammad Abu-Elmagd, Stephen W. Scherer

Research output: Contribution to journalArticle

Abstract

Background: We report a consanguineous couple that has experienced three consecutive pregnancy losses following the foetal ultrasound finding of short limbs. Post-termination examination revealed no skeletal dysplasia, but some subtle proximal limb shortening in two foetuses, and a spectrum of mildly dysmorphic features. Karyotype was normal in all three foetuses (46, XX) and comparative genomic hybridization microarray analysis detected no pathogenic copy number variants. Results: Whole-exome sequencing and genome-wide homozygosity mapping revealed a previously reported frameshift mutation in the OBSL1 gene (c.1273insA p.T425nfsX40), consistent with a diagnosis of 3-M Syndrome 2 (OMIM #612921), which had not been anticipated from the clinical findings. Conclusions: Our study provides novel insight into the early clinical manifestations of this form of 3-M syndrome, and demonstrates the utility of whole exome sequencing as a tool for prenatal diagnosis in particular when there is a family history suggestive of a recurrent set of clinical symptoms.

Original languageEnglish (US)
Article numberS12
JournalBMC genomics
Volume16
Issue number1
DOIs
StatePublished - Jan 15 2015

Keywords

  • 3-M Syndrome
  • Exome sequencing
  • Frameshift mutation
  • OBSL1
  • Skeletal dysplasia

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

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    Marshall, C. R., Farrell, S. A., Cushing, D., Paton, T., Stockley, T. L., Stavropoulos, D. J., Ray, P. N., Szego, M., Lau, L., Pereira, S. L., Cohn, R. D., Wintle, R. F., Abuzenadah, A. M., Abu-Elmagd, M., & Scherer, S. W. (2015). Whole-exome analysis of foetal autopsy tissue reveals a frameshift mutation in OBSL1, consistent with a diagnosis of 3-M Syndrome. BMC genomics, 16(1), [S12]. https://doi.org/10.1186/1471-2164-16-S1-S12