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Título
High prevalence of variants in skeletal dysplasia associated genes in individuals with short stature and minor skeletal anomalies
Autor(es)
Materia
Endocrinología
Clasificación UNESCO
3205.02 Endocrinología
Fecha de publicación
2021
Citación
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, Travessa AM, González de Buitrago Amigo J, Del Pozo A, Vallespín E, Solís M, Goetz C, Campos-Barros Á, Santos-Simarro F, González-Casado I, Ros-Pérez P, Parrón-Pajares M, Heath KE. High prevalence of variants in skeletal dysplasia associated genes in individuals with short stature and minor skeletal anomalies. Eur J Endocrinol. 2021 Oct 11;185(5):691-705
Resumen
[EN]Objective: Next generation sequencing (NGS) has expanded the diagnostic paradigm turning the focus to the growth plate.
The aim of the study was to determine the prevalence of variants in genes implicated in skeletal dysplasias in probands
with short stature and mild skeletal anomalies.
Design: Clinical and radiological data were collected from 108 probands with short stature and mild skeletal anomalies.
Methods: A customized skeletal dysplasia NGS panel was performed. Variants were classified using ACMG
recommendations and Sherloc. Anthropometric measurements and skeletal anomalies were subsequently compared in
those with or without an identified genetic defect.
Results: Heterozygous variants were identified in 21/108 probands (19.4%). Variants were most frequently identified
in ACAN (n = 10) and IHH (n = 7) whilst one variant was detected in COL2A1, CREBBP, EXT1, and PTPN11. Statistically
significant differences (P < 0.05) were observed for sitting height/height (SH/H) ratio, SH/H ratio standard deviation
score (SDS), and the SH/H ratio SDS >1 in those with an identified variant compared to those without.
Conclusions: A molecular defect was elucidated in a fifth of patients. Thus, the prevalence of mild forms of skeletal
dysplasias is relatively high in individuals with short stature and mild skeletal anomalies, with variants in ACAN and
IHH accounting for 81% of the cases. An elevated SH/H ratio appears to be associated with a greater probability in
detecting a variant, but no other clinical or radiological feature has been found determinant to finding a genetic cause.
Currently, we cannot perform extensive molecular studies in all short stature individuals so detailed clinical and
radiological phenotyping may orientate which are the candidate patients to obtain worthwhile
results. In addition, detailed phenotyping of probands and family members will often
aid variant classification.
URI
ISSN
0804-4643
DOI
10.1530/EJE-21-0557
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