학술논문
Familial Short Stature--A Novel Phenotype of Growth Plate Collagenopathies
Clinical Research Article
Clinical Research Article
Document Type
Academic Journal
Author
Source
Journal of Clinical Endocrinology & Metabolism. June 2021, Vol. 106 Issue 6, p1742, 8 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Collagens are the most abundant proteins in the human body. They play an important structural role and by interacting with cellular receptors, they also participate in the regulation of cell [...]
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 [less than or equal to] -2 SD both in the patient and his or her shorter parent) treated with GH were included in the study. Nextgeneration 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. Key Words: familial short stature, growth plate, collagenopathies, next-generation sequencing, growth hormone treatment
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 [less than or equal to] -2 SD both in the patient and his or her shorter parent) treated with GH were included in the study. Nextgeneration 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. Key Words: familial short stature, growth plate, collagenopathies, next-generation sequencing, growth hormone treatment