ArticleHuman molecular genetics2017
Klinefelter syndrome comorbidities linked to increased X chromosome gene dosage and altered protein interactome activity.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses 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
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 98 citations in OpenAlex.
- Sex chromosome aneuploidy impacts on human gene expression and regulation: a systematic review.Molecular medicine (Cambridge, Mass.) · 2025Pooled it
- A systematic review of core outcomes reported in boys and men with Klinefelter syndrome.Endocrine · 2025Pooled it
- Article
- Natural History of Prenatally Identified Children with 48,XXYY Syndrome in Infancy and Early Childhood.medRxiv : the preprint server for health sciences · 2026Article
- A clinical protocol for the detection of comorbidities associated with monogenic causes of male infertility.Human reproduction (Oxford, England) · 2026Article
- Epigenetic Clock Analysis of Sex Chromosome Aneuploidies.Aging cell · 2025Article
- An iPSC-based model of 47,XYY Jacobs syndrome reveals a DNA methylation-independent transcriptional dysregulation shared with male X aneuploid cells.Genome research · 2025Article
- Diabetic Ketoacidosis in Klinefelter Syndrome Sans Malignancy with Unusually Elevated Levels of CEA: A Case Report.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Integration of long-read sequencing, DNA methylation and gene expression reveals heterogeneity in Y chromosome segment lengths in phenotypic males with 46,XX testicular disorder/difference of sex development.Biology of sex differences · 2024Article
- The testicular microvasculature in Klinefelter syndrome is immature with compromised integrity and characterized by excessive inflammatory cross-talk.Human reproduction (Oxford, England) · 2023Article
- The multi-omic landscape of sex chromosome abnormalities: current status and future directions.Endocrine connections · 2023Review
- Dosage of the pseudoautosomal gene SLC25A6 is implicated in QTc interval duration.Scientific reports · 2023Article
- Reproductive hormones, bone mineral content, body composition, and testosterone therapy in boys and adolescents with Klinefelter syndrome.Endocrine connections · 2023Article
- Individuals with numerical and structural variations of sex chromosomes: interdisciplinary management with focus on fertility potential.Frontiers in endocrinology · 2023Review
- Integrative epigenome profiling of 47XXY provides insights into whole genomic DNA hypermethylation and active chromatin accessibility.Frontiers in molecular biosciences · 2023Article
- Transcriptomic differences between fibrotic and non-fibrotic testicular tissue reveal possible key players in Klinefelter syndrome-related testicular fibrosis.Scientific reports · 2022Article
- KIF2C affects sperm cell differentiation in patients with Klinefelter syndrome, as revealed by RNA-Seq and scRNA-Seq data.FEBS open bio · 2022Article
- Article
- Sex chromosome aneuploidies give rise to changes in the circular RNA profile: A circular transcriptome-wide study of Turner and Klinefelter syndrome across different tissues.Frontiers in genetics · 2022Article
- Update on genetic screening and treatment for infertile men with genetic disorders in the era of assisted reproductive technology.Clinical and experimental reproductive medicine · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Klinefelter syndrome (KS) (47,XXY) is the most common male sex chromosome aneuploidy. Diagnosis and clinical supervision remain a challenge due to varying phenotypic presentation and insufficient characterization of the syndrome. Here we combine health data-driven epidemiology and molecular level systems biology to improve the understanding of KS and the molecular interplay influencing its comorbidities. In total, 78 overrepresented KS comorbidities were identified using in- and out-patient registry data from the entire Danish population covering 6.8 million individuals. The comorbidities extracted included both clinically well-known (e.g. infertility and osteoporosis) and still less established KS comorbidities (e.g. pituitary gland hypofunction and dental caries). Several systems biology approaches were applied to identify key molecular players underlying KS comorbidities: Identification of co-expressed modules as well as central hubs and gene dosage perturbed protein complexes in a KS comorbidity network build from known disease proteins and their protein-protein interactions. The systems biology approaches together pointed to novel aspects of KS disease phenotypes including perturbed Jak-STAT pathway, dysregulated genes important for disturbed immune system (IL4), energy balance (POMC and LEP) and erythropoietin signalling in KS. We present an extended epidemiological study that links KS comorbidities to the molecular level and identify potential causal players in the disease biology underlying the identified comorbidities.
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.