Dataset Information

Clinical Profiles and Genetic Spectra of 814 Chinese Children With Short Stature.

ABSTRACT:

Context

Data and studies based on exome sequencing for the genetic evaluation of short stature are limited, and more large-scale studies are warranted. Some factors increase the likelihood of a monogenic cause of short stature, including skeletal dysplasia, severe short stature, and small for gestational age (SGA) without catch-up growth. However, whether these factors can serve as predictors of molecular diagnosis remains unknown.

Objective

We aimed to explore the diagnostic efficiency of the associated risk factors and their exome sequences for screening.

Methods

We defined and applied factors that increased the likelihood of monogenic causes of short stature in diagnostic genetic tests based on next-generation sequencing (NGS) in 814 patients with short stature and at least 1 other factor.

Results

Pathogenic/likely pathogenic (P/LP) variants in genes, copy number variations, and chromosomal abnormalities were identified in 361 patients. We found P/LP variants among 111 genes, and RASopathies comprised the most important etiology. Short stature combined with other phenotypes significantly increased the likelihood of a monogenic cause, including skeletal dysplasia, facial dysmorphism, and intellectual disability, compared with simple severe short stature (<-3 SD scores). We report novel candidate pathogenic genes, KMT2C for unequivocal growth hormone insensitivity and GATA6 for SGA.

Conclusion

Our study identified the diagnostic characteristics of NGS in short stature with different risk factors. Our study provides novel insights into the current understanding of the etiology of short stature in patients with different phenotypes.

SUBMITTER: Li X

PROVIDER: S-EPMC8947318 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical Profiles and Genetic Spectra of 814 Chinese Children With Short Stature.

Li Xin X Yao Ruen R Chang Guoying G Li Qun Q Song Cui C Li Niu N Ding Yu Y Li Juan J Chen Yao Y Wang Yirou Y Huang Xiaodong X Shen Yongnian Y Zhang Hao H Wang Jian J Wang Xiumin X

The Journal of clinical endocrinology and metabolism 20220301 4

<h4>Context</h4>Data and studies based on exome sequencing for the genetic evaluation of short stature are limited, and more large-scale studies are warranted. Some factors increase the likelihood of a monogenic cause of short stature, including skeletal dysplasia, severe short stature, and small for gestational age (SGA) without catch-up growth. However, whether these factors can serve as predictors of molecular diagnosis remains unknown.<h4>Objective</h4>We aimed to explore the diagnostic effi ...[more]

PMID: 34850017

Similar Datasets

Project description:BackgroundElevated triglyceride (TG) levels are a biomarker for cardiovascular disease (CVD) risk. The correlation between serum uric acid (SUA) and TG concentrations in adults or obese children is well established. However, studies on SUA and TG in children with short stature are limited.AimTo determine the relationship between SUA and TG levels in short children and adolescents.MethodThis was a cross-sectional evaluation of a cohort of 1095 patients with short stature (720 males and 375 females). The related clinical characteristics, including anthropometric and biochemical parameters, were determined.ResultsSmooth curve fitting, adjusted for potential confounders was performed, which indicated the existence of a non-linear relationship between these measures. Piecewise multivariate linear analysis revealed a significant positive relationship between SUA and TG at SUA concentrations over 7 mg/dL (β = 0.13, 95% CI: 0.05-0.22, P = 0.002) but no significant correlation at lower SUA levels (β = 0.01, 95% CI: 0.01-0.04, P = 0.799). Furthermore, a stratified analysis was performed to appraise changes in this relationship for different sexes and standard deviation levels of body mass index (BMI). The non-linear relationship remained consistent in males and females with BMI standard deviation scores (BMI SDS) ≥ 0, with inflection points of 6.71 mg/dL and 3.93 mg/dL, respectively. Within these two groups, SUA and TG levels showed a positive association when SUA levels were higher than the inflection point (β = 0.21, 95% CI: 0.11-0.31, P < 0.001 for males and β = 0.1, 95% CI: 0.03-0.17, P = 0.005 for females). However, a specific relationship was not observed at lower SUA levels. No significant relationships were found between SUA and TG levels in males and females with BMI SDS < 0.ConclusionThe present study identified the non-linear association of SUA and TG levels with short children and adolescents. This relationship was based on BMI status. This finding suggests that health status should be considered for short stature children with high SUA levels, especially in children with a high BMI standard deviation score.

Dataset Information

Clinical Profiles and Genetic Spectra of 814 Chinese Children With Short Stature.

Context

Objective

Methods

Results

Conclusion

Publications

Clinical Profiles and Genetic Spectra of 814 Chinese Children With Short Stature.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets