Large-Scale Pooled Next-Generation Sequencing of 1077 Genes to Identify Genetic Causes of Short Stature

Context: The majority of patients presenting with short stature do not receive a definitive diagnosis. Advances in genetic sequencing allow for large-scale screening of candidate genes, potentially leading to genetic diagnoses. Objectives: The purpose of this study was to discover genetic variants that contribute to short stature in a cohort of children with no known genetic etiology. Design: This was a prospective cohort study of subjects with short stature. Setting: The setting was a pediatric endocrinology and genetics clinics at an academic center. Patients: A total of 192 children with short stature with no defined genetic etiology and 192 individuals of normal stature from the Framingham Heart Study were studied. Intervention: Pooled targeted sequencing using next-generation DNA sequencing technology of the exons of 1077 candidate genes was performed. Main Outcome Measures: The numbers of rare nonsynonymous genetic variants found in case patients but not in control subjects, known pathogenic variant...