title: Whole exome sequencing to identify genetic causes of short stature.
abstract: OBJECTIVE
  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.
authors: Department of Genetics, Harvard Medical School, Boston, Mass., USA.
authors: Michael H
authors: MH
authors: Guo
authors: Yiping
authors: Y
authors: Shen
authors: Emily C
authors: EC
authors: Walvoord
authors: Timothy C
authors: TC
authors: Miller
authors: Jennifer E
authors: JE
authors: Moon
authors: Joel N
authors: JN
authors: Hirschhorn
authors: Andrew
authors: A
authors: Dauber
mesh_terms: D002648:Child; D002675:Child, Preschool; D059472:Exome; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D055106:Genome-Wide Association Study; D006130:Growth Disorders / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male