ArticleThe Journal of clinical endocrinology and metabolism2013
Large-scale pooled next-generation sequencing of 1077 genes to identify genetic causes of short stature.
Article in The Journal of clinical endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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Who cites it
38 citing papers in PubMed, 83 citations in OpenAlex.
- Whole exome sequencing to identify genetic causes of short stature.Hormone research in paediatrics · 2014Trial
- Healthy short stature.Archives of endocrinology and metabolism · 2026Review
- Optimising diagnosis in children with short stature: an integrated clinical and NGS approach.Endocrine connections · 2025Article
- Role of genetic investigation in the diagnosis of short stature in a cohort of Italian children.Journal of endocrinological investigation · 2024Article
- Clinical profiles and molecular genetic analyses of 98 Chinese children with short statures.Frontiers in genetics · 2024Article
- Exploring the Genetic Causes for Postnatal Growth Failure in Children Born Non-Small for Gestational Age.Journal of clinical medicine · 2023Article
- Association of rare, recurrent nonsynonymous variants in the germline of prostate cancer patients of African ancestry.The Prostate · 2023Article
- A Genetic Approach in the Evaluation of Short Stature.The Eurasian journal of medicine · 2022Article
- Diagnostic yield of a multigene sequencing approach in children classified as idiopathic short stature.Endocrine connections · 2022Article
- Balanced assessment of growth disorders using clinical, endocrinological, and genetic approaches.Annals of pediatric endocrinology & metabolism · 2021Article
- Clinical relevance of targeted exome sequencing in patients with rare syndromic short stature.Orphanet journal of rare diseases · 2021Article
- Focused Revision: ACMG practice resource: Genetic evaluation of short stature.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Growth failure: 'idiopathic' only after a detailed diagnostic evaluation.Endocrine connections · 2021Review
- Rare CNVs provide novel insights into the molecular basis of GH and IGF-1 insensitivity.European journal of endocrinology · 2020Article
- Novel Mutations and Genes That Impact on Growth in Short Stature of Undefined Aetiology: The EPIGROW Study.Journal of the Endocrine Society · 2020Article
- In Silico Structural and Biochemical Functional Analysis of a NovelInternational journal of molecular sciences · 2020Article
- Contribution of gene mutations to Silver-Russell syndrome phenotype: multigene sequencing analysis in 92 etiology-unknown patients.Clinical epigenetics · 2020Article
- A Novel Mutation in Insulin-Like Growth Factor 1 Receptor (c.641-2A>G) Is Associated with Impaired Growth, Hypoglycemia, and Modified Immune Phenotypes.Hormone research in paediatrics · 2020Article
- Molecular and clinical analyses of two patients with UPD(16)mat detected by screening 94 patients with Silver-Russell syndrome phenotype of unknown aetiology.Journal of medical genetics · 2019Article
- Genetic diagnosis of congenital hypopituitarism by a target gene panel: novel pathogenic variants in GLI2, OTX2 and GHRHR.Endocrine connections · 2019Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
contextThe majority of patients presenting with short stature do not receive a definitive diagnosis. Advances in genetic sequencing allow for large-scale screening of candidate genes, potentially leading to genetic diagnoses.
objectivesThe purpose of this study was to discover genetic variants that contribute to short stature in a cohort of children with no known genetic etiology.
designThis was a prospective cohort study of subjects with short stature.
settingThe setting was a pediatric endocrinology and genetics clinics at an academic center. PATIENTS: A total of 192 children with short stature with no defined genetic etiology and 192 individuals of normal stature from the Framingham Heart Study were studied.
interventionPooled targeted sequencing using next-generation DNA sequencing technology of the exons of 1077 candidate genes was performed.
main outcome measuresThe numbers of rare nonsynonymous genetic variants found in case patients but not in control subjects, known pathogenic variants in case patients, and potentially pathogenic variants in IGF1R were determined.
resultsWe identified 4928 genetic variants in 1077 genes that were present in case patients but not in control subjects. Of those, 1349 variants were novel (898 nonsynonymous). False-positive rates from pooled sequencing were 4% to 5%, and the false-negative rate was 0.1% in regions covered well by sequencing. We identified 3 individuals with known pathogenic variants in PTPN11 causing undiagnosed Noonan syndrome. There were 9 rare potentially nonsynonymous variants in IGF1R, one of which is a novel, probably pathogenic, frameshift mutation. A previously reported pathogenic variant in IGF1R was present in a control subject.
conclusionsLarge-scale sequencing efforts have the potential to rapidly identify genetic etiologies of short stature, but data interpretation is complex. Noonan syndrome may be an underdiagnosed cause of short stature.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.