ArticleThe Journal of clinical endocrinology and metabolism2018
HS6ST1 Insufficiency Causes Self-Limited Delayed Puberty in Contrast With Other GnRH Deficiency Genes.
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 26 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Pooled it
- Circulating markers of NADH-reductive stress correlate with mitochondrial disease severity.The Journal of clinical investigation · 2021Trial
- Combined HS6ST1 and HS6ST2 loss disrupts the formation and migration of gonadotropin-releasing hormone neurons.Development (Cambridge, England) · 2026Article
- Neurotrophic Control of Puberty: From Molecular Signaling to Disorders of Pubertal Timing.Current issues in molecular biology · 2025Review
- Contributions of Common Genetic Variants to Constitutional Delay of Puberty and Idiopathic Hypogonadotropic Hypogonadism.The Journal of clinical endocrinology and metabolism · 2024Article
- Genetic variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfate diversity.Essays in biochemistry · 2024Review
- Prevalence of Deleterious Variants in MC3R in Patients With Constitutional Delay of Growth and Puberty.The Journal of clinical endocrinology and metabolism · 2023Article
- Convergent biological pathways underlying the Kallmann syndrome-linked genes Hs6st1 and Fgfr1.Human molecular genetics · 2022Article
- Genetics of pubertal delay.Clinical endocrinology · 2022Review
- Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation.International journal of molecular sciences · 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
- A recessive PRDM13 mutation results in congenital hypogonadotropic hypogonadism and cerebellar hypoplasia.The Journal of clinical investigation · 2021Article
- Genetic evaluation supports differential diagnosis in adolescent patients with delayed puberty.European journal of endocrinology · 2021Article
- Epigenomic and transcriptomic analyses reveal early activation of the HPG axis in in vitro-produced male dairy calves.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- The Differential Roles for Neurodevelopmental and Neuroendocrine Genes in Shaping GnRH Neuron Physiology and Deficiency.International journal of molecular sciences · 2021Review
- Timing of Pubertal Onset in Girls and Boys With Constitutional Delay.The Journal of clinical endocrinology and metabolism · 2021Article
- Genetics of congenital hypogonadotropic hypogonadism: peculiarities and phenotype of an oligogenic disease.Human genetics · 2021Review
- DLG2 variants in patients with pubertal disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Article
- LGR4 deficiency results in delayed puberty through impaired Wnt/β-catenin signaling.JCI insight · 2020Article
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 5 institutions in 3 countries.
Funding
Abstract
Context: Self-limited delayed puberty (DP) segregates in an autosomal-dominant pattern, but the genetic basis is largely unknown. Although DP is sometimes seen in relatives of patients with hypogonadotropic hypogonadism (HH), mutations in genes known to cause HH that segregate with the trait of familial self-limited DP have not yet been identified. Objective: To assess the contribution of mutations in genes known to cause HH to the phenotype of self-limited DP. Design, Patients, and Setting: We performed whole-exome sequencing in 67 probands and 93 relatives from a large cohort of familial self-limited DP, validated the pathogenicity of the identified gene variant in vitro, and examined the tissue expression and functional requirement of the mouse homolog in vivo. Results: A potentially pathogenic gene variant segregating with DP was identified in 1 of 28 known HH genes examined. This pathogenic variant occurred in HS6ST1 in one pedigree and segregated with the trait in the six affected members with heterozygous transmission (P = 3.01 × 10-5). Biochemical analysis showed that this mutation reduced sulfotransferase activity in vitro. Hs6st1 mRNA was expressed in peripubertal wild-type mouse hypothalamus. GnRH neuron counts were similar in Hs6st1+/- and Hs6st1+/+ mice, but vaginal opening was delayed in Hs6st1+/- mice despite normal postnatal growth. Conclusions: We have linked a deleterious mutation in HS6ST1 to familial self-limited DP and show that heterozygous Hs6st1 loss causes DP in mice. In this study, the observed overlap in potentially pathogenic mutations contributing to the phenotypes of self-limited DP and HH was limited to this one gene.
Indexed as
Identifiers
What OpenQuestion holds
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.