Whole exome sequencing to identify genetic causes of short stature

Michael H. Guo, Yiping Shen, Emily C. Walvoord, Timothy C. Miller, Jennifer E. Moon, Joel N. Hirschhorn, Andrew Dauber

Research output: Contribution to journalArticle

37 Scopus citations


Background/Aims: Short stature is a common reason for presentation to pediatric endocrinology clinics. However, for most patients, no cause for the short stature can be identified. As genetics plays a strong role in height, we sought to identify known and novel genetic causes of short stature. Methods: We recruited 14 children with severe short stature of unknown etiology. We conducted whole exome sequencing of the patients and their family members. We used an analysis pipeline to identify rare non-synonymous genetic variants that cause the short stature. Results: We identified a genetic cause of short stature in 5 of the 14 patients. This included cases of floating-harbor syndrome, Kenny-Caffey syndrome, the progeroid form of Ehlers-Danlos syndrome, as well as 2 cases of the 3-M syndrome. For the remaining patients, we have generated lists of candidate variants. Conclusions: Whole exome sequencing can help identify genetic causes of short stature in the context of defined genetic syndromes, but may be less effective in identifying novel genetic causes of short stature in individual families. Utilized in the clinic, whole exome sequencing can provide clinically relevant diagnoses for these patients. Rare syndromic causes of short stature may be underrecognized and underdiagnosed in pediatric endocrinology clinics.

Original languageEnglish (US)
Pages (from-to)44-52
Number of pages9
JournalHormone Research in Paediatrics
Issue number1
StatePublished - Jul 2014


  • Growth disorder
  • Growth hormone
  • Short stature
  • Skeletal dysplasia
  • Whole exome sequencing

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

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  • Cite this

    Guo, M. H., Shen, Y., Walvoord, E. C., Miller, T. C., Moon, J. E., Hirschhorn, J. N., & Dauber, A. (2014). Whole exome sequencing to identify genetic causes of short stature. Hormone Research in Paediatrics, 82(1), 44-52. https://doi.org/10.1159/000360857