Abstract | BACKGROUND: Syndromic short stature is a genetic and phenotypic heterogeneous disorder with multiple causes. 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. METHODS: 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. RESULTS: Of the seven patients, three pathogenic/likely pathogenic gene mutations, including one FGFR3 mutation (c.1620C>A p.N540K), one novel GNAS mutation (c.2288C>T p.A763V), and one novel TRPS1 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 FGFR3 mutation, a female 4 and 3/12 years of age, was diagnosed with hypochondroplasia. Long-acting growth hormone improved her height from 85.8 cm [- 5.05 standard deviation (SD)] to 100.4 cm (- 4.02 SD), and her increased height SD score (SDS) was 1.03 after 25 months of treatment. The proband with a GNAS mutation, a female 12 and 9/12 years of age, was diagnosed with pseudohypoparathyroidism Ia. After 14 months of treatment with short-acting growth hormone, her height improved from 139.3 cm (- 2.69 SD) to 145.0 cm (- 2.36 SD), and her increased height SDS was 0.33. CONCLUSIONS:
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Authors | Huihui Sun, Na Li, Naijun Wan |
Journal | BMC medical genomics
(BMC Med Genomics)
Vol. 14
Issue 1
Pg. 261
(11 05 2021)
ISSN: 1755-8794 [Electronic] England |
PMID | 34740356
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2021. The Author(s). |
Chemical References |
- Growth Hormone
- FGFR3 protein, human
- Receptor, Fibroblast Growth Factor, Type 3
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Topics |
- Body Height
(genetics)
- Bone and Bones
(abnormalities)
- Child
- Child, Preschool
- Dwarfism
(drug therapy)
- Female
- Growth Hormone
(therapeutic use)
- Humans
- Limb Deformities, Congenital
(drug therapy)
- Lordosis
(drug therapy)
- Male
- Phenotype
- Pseudohypoparathyroidism
(drug therapy)
- Receptor, Fibroblast Growth Factor, Type 3
(genetics)
- Exome Sequencing
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