RT Journal Article
T1 High prevalence of variants in skeletal dysplasia associated genes in individuals with short stature and minor skeletal anomalies
A1 Sentchordi-Montane, Lucia
A1 Benito-Sanz, Sara
A1 Aza-Carmona, Miriam
A1 Diaz-Gonzalez, Francisca
A1 Modamio-Hoybjor, Silvia
A1 de la Torre, Carolina
A1 Nevado, Julian
A1 Ruiz-Ocana, Pablo
A1 Bezanilla-Lopez, Carolina
A1 Prieto, Pablo
A1 Bahillo-Curieses, Pilar
A1 Carcavilla, Atilano
A1 Mulero-Collantes, Ines
A1 Barreda-Bonis, Ana C.
A1 Cruz-Rojo, Jaime
A1 Ramirez-Fernandez, Joaquin
A1 Bermudez de la Vega, Jose Antonio
A1 Travessa, Andre M.
A1 de Buitrago Amigo, Jesus Gonzalez
A1 Del Pozo, Angela
A1 Vallespin, Elena
A1 Solis, Mario
A1 Goetz, Carlos
A1 Campos-Barros, Angel
A1 Santos-Simarro, Fernando
A1 Gonzalez-Casado, Isabel
A1 Ros-Perez, Purificacion
A1 Parron-Pajares, Manuel
A1 Heath, Karen E.
K1 Rubinstein-taybi-syndrome
K1 Idiopathic short stature
K1 Par1 deletion
K1 Growth
K1 Mutations
K1 Identification
K1 Disorders
K1 Missense
K1 Children
AB 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 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 INN 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 European Journal of aid variant classification.
PB Bioscientifica ltd
SN 0804-4643
YR 2021
FD 2021-11-01
LK https://hdl.handle.net/10668/25214
UL https://hdl.handle.net/10668/25214
LA en
DS RISalud
RD Apr 5, 2025