ArticleThe Journal of clinical endocrinology and metabolism2018
Contributions of Function-Altering Variants in Genes Implicated in Pubertal Timing and Body Mass for Self-Limited Delayed Puberty.
Article in The Journal of clinical endocrinology and metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Deleterious variants in intolerant genes reveal new candidates for self-limited delayed puberty.European journal of endocrinology · 2025Article
- Association of childhood dehydroepiandrosterone sulfate concentration, pubertal development, and DNA methylation at puberty-related genes.European journal of endocrinology · 2024Article
- Lack of a genetic risk continuum between pubertal timing in the general population and idiopathic hypogonadotropic hypogonadism.Journal of neuroendocrinology · 2024Article
- FTO-mediated mCommunications biology · 2023Article
- Molecular basis of normal and pathological puberty: from basic mechanisms to clinical implications.The lancet. Diabetes & endocrinology · 2023Review
- Effects of high-fat diet and treadmill running on the hypothalamic Kiss-1-GPR54 signaling pathway in male growing rats.Hormones (Athens, Greece) · 2022Article
- Genetics of pubertal delay.Clinical endocrinology · 2022Review
- Article
- Genetics of pubertal timing.Best practice & research. Clinical endocrinology & metabolism · 2022Review
- Genetic, epigenetic and enviromental influencing factors on the regulation of precocious and delayed puberty.Frontiers in endocrinology · 2022Review
- Genetic architecture of self-limited delayed puberty and congenital hypogonadotropic hypogonadism.Frontiers in endocrinology · 2022Review
- Whole exome sequencing identifies deleterious rare variants in CCDC141 in familial self-limited delayed puberty.NPJ genomic medicine · 2021Article
- Genetic evaluation supports differential diagnosis in adolescent patients with delayed puberty.European journal of endocrinology · 2021Article
- Unravelling the role of epigenetics in reproductive adaptations to early-life environment.Nature reviews. Endocrinology · 2020Review
- LGR4 deficiency results in delayed puberty through impaired Wnt/β-catenin signaling.JCI insight · 2020Article
- Genetic Evaluation of Patients With Delayed Puberty and Congenital Hypogonadotropic Hypogonadism: Is it Worthy of Consideration?Frontiers in endocrinology · 2020Review
- Delayed Puberty-Phenotypic Diversity, Molecular Genetic Mechanisms, and Recent Discoveries.Endocrine reviews · 2019Review
- The Genetic Basis of Delayed Puberty.Frontiers in endocrinology · 2019Review
- Genes underlying delayed puberty.Molecular and cellular endocrinology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
Context: Self-limited delayed puberty (DP) is often associated with a delay in physical maturation, but although highly heritable the causal genetic factors remain elusive. Genome-wide association studies of the timing of puberty have identified multiple loci for age at menarche in females and voice break in males, particularly in pathways controlling energy balance. Objective/Main Outcome Measures: We sought to assess the contribution of rare variants in such genes to the phenotype of familial DP. Design/Patients: We performed whole-exome sequencing in 67 pedigrees (125 individuals with DP and 35 unaffected controls) from our unique cohort of familial self-limited DP. Using a whole-exome sequencing filtering pipeline one candidate gene [fat mass and obesity-associated gene (FTO)] was identified. In silico, in vitro, and mouse model studies were performed to investigate the pathogenicity of FTO variants and timing of puberty in FTO+/- mice. Results: We identified potentially pathogenic, rare variants in genes in linkage disequilibrium with genome-wide association studies of age at menarche loci in 283 genes. Of these, five genes were implicated in the control of body mass. After filtering for segregation with trait, one candidate, FTO, was retained. Two FTO variants, found in 14 affected individuals from three families, were also associated with leanness in these patients with DP. One variant (p.Leu44Val) demonstrated altered demethylation activity of the mutant protein in vitro. Fto+/- mice displayed a significantly delayed timing of pubertal onset (P < 0.05). Conclusions: Mutations in genes implicated in body mass and timing of puberty in the general population may contribute to the pathogenesis of self-limited DP.
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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.