ESPE2024 Poster Category 1 Growth and Syndromes 1 (10 abstracts)
Comparison of the diagnostic yield of whole exome sequencing (WES) and targeted panel sequencing for children with idiopathic short stature (ISS)
Laurana Cellin 1 , Nathalia Andrade 1 , Alexsandra Malaquias 2 , Raissa Rezende 1 , Patricia Atique 3 , Camila Luz 4 , Gabriela Vasques 1 , Vinicius Souza 1 , Elisangela Quedas 1 , Sonir Antonini 3 , Paulo Collet-Solberg 4 , Renata Scalco 1 , Carlos Longui 2 & Alexander Jorge 1
1University of Sao Paulo, Sao Paulo, Brazil. 2Irmandade da Santa Casa de Misericórdia de São Paulo, Sao Paulo, Brazil. 3University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. 4Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
Introduction: Growth disorders are often caused by monogenic conditions, and genetic investigation should be guided by clinical findings. However, in children with ISS, the absence of specific clinical features prevents the candidate gene approach. ACMG practice guideline (2021) recommends that children with ISS could be evaluated using targeted panel sequencing or WES. In commercial laboratories, WES is often performed and the genetic evaluation is offered as a panel, facilitating analysis and interpretation. There are no studies that directly compare the diagnostic yield between WES and targeted panel analysis for children initially classified as ISS.
Objectives: To compare the diagnostic yield of WES with panels for the genetic diagnosis of children with ISS.
Methods: We sequentially enrolled 165 children with ISS and performed WES. We screened for rare and deleterious variants in genes associated with growth disorders and classified by ACMG/AMP criteria. Positive cases were those with pathogenic (P) or likely pathogenic (LP) variants in genes associated with growth disorders with compatible genotype-phenotype correlation. We included 25 targeted panel (14 commercials and 11 from research papers), with a median of 166 (IQR of 86 to 388) genes per panel. We applied each of these panels in our cohort to assess the diagnostic yield and compared with WES.
Results: We identified 22 P/LP variants, all of them in heterozygous state. Thirteen were in genes previously associated with ISS (SHOX, n = 5; ACAN n = 2; PTPN11 n = 2; IHH, NF1, BRAF and COL2A1, n = 1 each). Nine P/LP were identified in genes associated with more complex growth disorders but not previous involved in ISS phenotype (CSNK2A1, n = 2; THRA; PTHLH; ERF; POLR1A; RPL13; LTBP3; ZNF292, n = 1 each). Patient phenotype was reviewed and confirmed the absence of typical gene-phenotype association. WES had an overall diagnostic yield of 13.3%. When we analyzed our patients using the available short stature panels the average diagnosis rate was 7.3%, ranging from 1.2% to 10.3%. There was a positive correlation between the greater number of genes evaluated in the panels and the higher diagnosis rate (r =0.60, P = 0.001). Two genes were not included in any evaluated panel. Among the genes included less frequently in panels designed to evaluate short stature are those identified in rare forms of growth disorders, but no gene was present in all evaluated panels.
Conclusion: The use of WES improved the diagnostic yield compared to panels and better explains the genetic basis of isolated short stature phenotype.
Article tools
My recent searches
My recently viewed abstracts
Authors
ESPE Abstracts
© 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