Clinical and genetic evaluation of children with short stature of unknown origin

BMC Medical Genomics

Research Article

Qian Shao¹  Mei Zhang¹  Yanying Li¹  Bo Ban¹  Shuang Kou¹  Wanling Yang²  Chuanpeng Zhang³  Qianqian Zhao⁴ 

[1] Department of Endocrinology, Genetics and Metabolism, Affiliated Hospital of Jining Medical University, Jining Medical University, 89 Guhuai Road, 272029, Jining, Shandong, P.R. China;Chinese Research Center for Behavior Medicine in Growth and Development, 89 Guhuai Road, 272029, Jining, Shandong, P.R. China;Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, 999077, Hong Kong, P.R. China;Medical Research Center, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, 272029, Jining, Shandong, P.R. China;School of Medicine, Qingdao University, 266071, Qingdao, Shandong, P.R. China;Department of Endocrinology, Genetics and Metabolism, Affiliated Hospital of Jining Medical University, Jining Medical University, 89 Guhuai Road, 272029, Jining, Shandong, P.R. China;Chinese Research Center for Behavior Medicine in Growth and Development, 89 Guhuai Road, 272029, Jining, Shandong, P.R. China;

关键词: Short stature;    Whole-exome sequencing;    Genetic defects;    Mutation;    Clinical phenotypes;   

DOI  :  10.1186/s12920-023-01626-4

 received in 2022-06-29, accepted in 2023-08-02,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundShort stature is a common human trait. More severe and/or associated short stature is usually part of the presentation of a syndrome and may be a monogenic disease. The present study aimed to identify the genetic etiology of children with short stature of unknown origin.MethodsA total of 232 children with short stature of unknown origin from March 2013 to May 2020 were enrolled in this study. Whole exome sequencing (WES) was performed for the enrolled patients to determine the underlying genetic etiology.ResultsWe identified pathogenic or likely pathogenic genetic variants in 18 (7.8%) patients. All of these variants were located in genes known to be associated with growth disorders. Five of the genes are associated with paracrine signaling or cartilage extracellular matrix in the growth plate, including NPR2 (N = 1), ACAN (N = 1), CASR (N = 1), COMP (N = 1) and FBN1 (N = 1). Two of the genes are involved in the RAS/MAPK pathway, namely, PTPN11 (N = 6) and NF1 (N = 1). Two genes are associated with the abnormal growth hormone-insulin-like growth factor 1 (GH-IGF1) axis, including GH1 (N = 1) and IGF1R (N = 1). Two mutations are located in PROKR2, which is associated with gonadotropin-releasing hormone deficiency. Mutations were found in the remaining two patients in genes with miscellaneous mechanisms: ANKRD11 (N = 1) and ARID1A (N = 1).ConclusionsThe present study identified pathogenic or likely pathogenic genetic variants in eighteen of the 232 patients (7.8%) with short stature of unknown origin. Our findings suggest that in the absence of prominent malformation, genetic defects in hormones, paracrine factors, and matrix molecules may be the causal factors for this group of patients. Early genetic testing is necessary for accurate diagnosis and precision treatment.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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