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Milder forms may result from the combined effect of multiple genes; more severe short stature is suggestive of a monogenic condition. The etiology of most FSS cases has not been thoroughly elucidated to date.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To identify the genetic etiology of severe FSS in children treated with GH because of the diagnosis of small for gestational age or GH deficiency (SGA\/GHD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Settings, and Patients<\/jats:title><jats:p>Of 736 children treated with GH because of GHD\/SGA, 33 with severe FSS (life-minimum height \u22122.5 SD or less in both the patient and shorter parent) were included in the study. The genetic etiology was known in 5 of 33 children prior to the study [ACAN (in 2], NF1, PTPN11, and SOS1). In the remaining 28 of 33, whole-exome sequencing was performed. The results were evaluated using American College of Medical Genetics and Genomics standards and guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 30 of 33 children (90%), we found at least one variant with potential clinical significance in genes known to affect growth. A genetic cause was elucidated in 17 of 33 (52%). Of these children, variants in growth plate-related genes were found in 9 of 17 [COL2A1, COL11A1, and ACAN (all in 2), FLNB, FGFR3, and IGF1R], and IGF-associated proteins were affected in 2 of 17 (IGFALS and HMGA2). In the remaining 6 of 17, the discovered genetic mechanisms were miscellaneous (TRHR, MBTPS2, GHSR, NF1, PTPN11, and SOS1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Single-gene variants are frequent among families with severe FSS, with variants affecting the growth plate being the most prevalent.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2018-02288","type":"journal-article","created":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T22:06:56Z","timestamp":1549577216000},"page":"4273-4281","source":"Crossref","is-referenced-by-count":65,"title":["High Prevalence of Growth Plate Gene Variants in Children With Familial Short Stature Treated With GH"],"prefix":"10.1210","volume":"104","author":[{"given":"Lukas","family":"Plachy","sequence":"first","affiliation":[{"name":"Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic"},{"name":"University Hospital Motol, Prague 5, Czech 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