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This study aims to identify genetic causes in patients with syndromic short stature of unknown cause and evaluate the efficacy of the growth hormone response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Trio-whole-exome sequencing was applied to identify pathogenic gene mutations in seven patents with short stature, multiple malformations, and\/or intellectual disability. Whole-genome low-coverage sequencing was also performed to identify copy number variants in three patients with concurrent intellectual disability. Recombinant human growth hormone was administered to improve height in patients with an identified cause of syndromic short stature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the seven patients, three pathogenic\/likely pathogenic gene mutations, including one\n                      <jats:italic>FGFR3<\/jats:italic>\n                      mutation (c.1620C&gt;A p.N540K), one novel\n                      <jats:italic>GNAS<\/jats:italic>\n                      mutation (c.2288C&gt;T p.A763V), and one novel\n                      <jats:italic>TRPS1<\/jats:italic>\n                      mutation (c.2527_c.2528dupTA p.S843fsX72), were identified in three patients. No copy number variants were identified in the three patients with concurrent intellectual disability. The proband with an\n                      <jats:italic>FGFR3<\/jats:italic>\n                      mutation, a female 4 and 3\/12\u00a0years of age, was diagnosed with hypochondroplasia. Long-acting growth hormone improved her height from 85.8\u00a0cm [\u2212\u20095.05 standard deviation (SD)] to 100.4\u00a0cm (\u2212\u20094.02 SD), and her increased height SD score (SDS) was 1.03 after 25\u00a0months of treatment. The proband with a\n                      <jats:italic>GNAS<\/jats:italic>\n                      mutation, a female 12 and 9\/12\u00a0years of age, was diagnosed with pseudohypoparathyroidism Ia. After 14\u00a0months of treatment with short-acting growth hormone, her height improved from 139.3\u00a0cm (\u2212\u20092.69 SD) to 145.0\u00a0cm (\u2212\u20092.36 SD), and her increased height SDS was 0.33.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Trio-whole-exome sequencing was an important approach to confirm genetic disorders in patients with syndromic short stature of unknown etiology. Short-term growth hormone was effective in improving height in patients with hypochondroplasia and pseudohypoparathyroidism Ia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12920-021-01113-8","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T03:02:54Z","timestamp":1636081374000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Molecular genetic analysis and growth hormone response in patients with syndromic short stature"],"prefix":"10.1186","volume":"14","author":[{"given":"Huihui","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naijun","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"key":"1113_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1159\/000481777","volume":"89","author":"TK Homma","year":"2018","unstructured":"Homma TK, Krepischi ACV, Furuya TK, Honjo RS, Malaquias AC, Bertola DR, et al. 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