Familial Short Stature-A Novel Phenotype of Growth Plate Collagenopathies
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
33570564
DOI
10.1210/clinem/dgab084
PII: 6133323
Knihovny.cz E-resources
- Keywords
- collagenopathies, familial short stature, growth hormone treatment, growth plate, next-generation sequencing,
- MeSH
- Databases, Factual MeSH
- Child MeSH
- Adult MeSH
- Phenotype MeSH
- Genetic Association Studies MeSH
- Collagen Type XI genetics MeSH
- Collagen deficiency genetics MeSH
- Humans MeSH
- Human Growth Hormone deficiency therapeutic use MeSH
- Adolescent MeSH
- Young Adult MeSH
- Growth Disorders * drug therapy epidemiology genetics pathology MeSH
- Child, Preschool MeSH
- Retrospective Studies MeSH
- Growth Plate growth & development metabolism pathology MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic epidemiology MeSH
- Names of Substances
- COL11A1 protein, human MeSH Browser
- COL11A2 protein, human MeSH Browser
- Collagen Type XI MeSH
- Collagen MeSH
- Human Growth Hormone MeSH
CONTEXT: Collagens are the most abundant proteins in the human body. In a growth plate, collagen types II, IX, X, and XI are present. Defects in collagen genes cause heterogeneous syndromic disorders frequently associated with short stature. Less is known about oligosymptomatic collagenopathies. OBJECTIVE: This work aims to evaluate the frequency of collagenopathies in familial short stature (FSS) children and to describe their phenotype, including growth hormone (GH) treatment response. METHODS: Eighty-seven FSS children (pretreatment height ≤ -2 SD both in the patient and his or her shorter parent) treated with GH were included in the study. Next-generation sequencing was performed to search for variants in the COL2A1, COL9A1, COL9A2, COL9A3, COL10A1, COL11A1, and COL11A2 genes. The results were evaluated using American College of Medical Genetics and Genomics guidelines. The GH treatment response of affected children was retrospectively evaluated. RESULTS: A likely pathogenic variant in the collagen gene was found in 10 of 87 (11.5%) children. Detailed examination described mild asymmetry with shorter limbs and mild bone dysplasia signs in 2 of 10 and 4 of 10 affected children, respectively. Their growth velocity improved from a median of 5.3 cm/year to 8.7 cm/year after 1 year of treatment. Their height improved from a median of -3.1 SD to -2.6 SD and to -2.2 SD after 1 and 3 years of therapy, respectively. The final height reached by 4 of 10 children differed by -0.67 to +1.0 SD and -0.45 to +0.5 SD compared to their pretreatment height and their affected untreated parent's height, respectively. CONCLUSION: Oligosymptomatic collagenopathies are a frequent cause of FSS. The short-term response to GH treatment is promising.
References provided by Crossref.org
Monogenic causes of familial short stature
Etiology of combined pituitary hormone deficiency: GNAO1 as a novel candidate gene
Analysis of children with familial short stature: who should be indicated for genetic testing?
