ESPEYB19 4. Growth and Growth Factors New Perspectives (2 abstracts)
4.9. High prevalence of variants in skeletal dysplasia associated genes in individuals with short stature and minor skeletal anomalies
Sentchordi-Montané L , Benito-Sanz S , Aza-Carmona M , Díaz-González F , Modamio-Høybjør S , De la Torre C , Nevado J , Ruiz-Ocaña P , Bezanilla-López C , Prieto P , Bahíllo-Curieses P , Carcavilla A , Mulero-Collantes I , Barreda-Bonis AC , Cruz-Rojo J , Ramírez-Fernández J , Bermúdez de la Vega JA , Travess AM , González de Buitrago Amigo J , Del Pozo A , Vallespín E , Solís M , Goetz C , Campos-Barros A , Santos-Simarro F , González-Casado I , Ros-Pérez P , Parrón-Pajares M & Heath KE
Eur J Endocrinol, 2021. 185(5): p. 691-705. PMID: 34516402
Brief Summary: This study evaluated the prevalence of genetic variants in children with idiopathic short stature (ISS) using next-generation sequencing (NGS). Heterozygous variants in known genes involved in skeletal physiology were identified in almost 20% of children. The use of advanced genetic analysis techniques will lead to an increased identification of new genetic variants, expanding the knowledge on the pathogenesis of short stature.
Short stature is the most common cause of referral to pediatric endocrinologist. The application of next-generation sequencing (NGS) to children with unexplained short stature, known as idiopathic short stature (ISS), has unveiled many genetic variants associated with ISS (1). This study assessed the prevalence of genetic variants in a cohort of 108 children with severe ISS (mean height SDS: −2.97) and mild skeletal anomalies. Body disproportion was indicated by arm spam/height ratio (A/H) ratio ≤ 0.96 and/or sitting height/height (SH/H) ratio ≥ 0.55. SHOX mutations were excluded in all patients. A NGS skeletal panel, including ACAN, IHH, NPR2, FGFR3, COL2A1, and PTPN11, was applied. A total of 20 heterozygous variants were identified in 21/108 patients (19.4%), mostly ACAN (n = 10) and IHH (n = 7). Single variants were also found in COL2A1, CREBBP, EXT1, and PTPN11. Interestingly, only 2/10 patients with ACAN variants had advanced bone age. Out of 20 variants, 11 (55%) were classified as pathogenic and 17 (80.9%) were inherited. No pathogenic or likely pathogenic or VUS were identified in NPR2 or FGFR3 genes. Lower limb shortening (determined by the SH/H ratio) and paternal skeletal traits showed a high concordance with NGS results.
This study confirms previous reports showing that a high percentage of children with ISS, and especially those with mild skeletal traits, may harbor variants in genes involved in growth plate physiology. The Authors targeted specific skeletal dysplasia genes, and it is likely that the use of whole exome sequencing (WES) would identify even more genetic variants. The extensive use of WES will certainly lead to identify new genetic variants underlying ISS.
Reference: 1. Murray PG, Clayton PE, Chernausek SD. A genetic approach to evaluation of short stature of undetermined cause. Lancet Diabetes Endocrinol 2018;6:564–574.
Volume 19
Article tools
My recent searches
My recently viewed abstracts
Authors
ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more