ArticleThe Journal of clinical endocrinology and metabolism2022
Prevalence and Phenotypic Effects of Copy Number Variants in Isolated Hypogonadotropic Hypogonadism.
Article in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Reversal of Congenital Hypogonadotropic Hypogonadism.The Journal of clinical endocrinology and metabolism · 2026Pooled it
- Genetic landscape of a neonatal hypogonadotropic hypogonadism series: Novel variants and phenotypic spectrum.Journal of neuroendocrinology · 2026Article
- Olfactory dysfunction and submicroscopic abnormalities: unveiling hidden pathologies.Frontiers in molecular neuroscience · 2026Review
- De novo rare EMX2 variants lead to idiopathic hypogonadotropic hypogonadism.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Expanded Targeted-Exome Sequencing and Functional Validation Improve Molecular Diagnosis and Refine Genotype-Phenotype Correlations in Congenital Hypogonadotropic Hypogonadism.Neuroendocrinology · 2026Article
- Clinical approach to the male with delayed puberty.Archives of endocrinology and metabolism · 2025Review
- Expanding the phenotypic spectrum of PROK2/PROKR2: a recall-by-genotype study.Human genetics · 2025Article
- Expanding the Spectrum of Endocrine Abnormalities Associated With SOX11-related Disorders.The Journal of clinical endocrinology and metabolism · 2025Article
- Copy Number Variations of theGenes · 2025Article
- Genome sequencing reveals novel causative structural and single nucleotide variants in Pakistani families with congenital hypogonadotropic hypogonadism.BMC genomics · 2024Article
- Defective FGFR1 Signaling Disrupts Glucose Regulation: Evidence From Humans WithJournal of the Endocrine Society · 2024Article
- Variety of genetic defects in GnRH and hypothalamic-pituitary signaling and development in normosmic patients with IHH.Frontiers in endocrinology · 2024Article
- Genetic architecture of congenital hypogonadotropic hypogonadism: insights from analysis of a Portuguese cohort.Human reproduction open · 2024Article
- Applications of genomic research in pediatric endocrine diseases.Clinical and experimental pediatrics · 2023Article
- Mutation spectrum and frequency of copy number variations of the ANOS1 gene in patients with Kallmann syndrome or normosmic isolated hypogonadotropic hypogonadism.Endocrine connections · 2023Article
- Reproductive Phenotypes and Genotypes in Men With IHH.The Journal of clinical endocrinology and metabolism · 2023Article
- Heterozygous mutations in SOX2 may cause idiopathic hypogonadotropic hypogonadism via dominant-negative mechanisms.JCI insight · 2023Article
- Prevalence and Phenotypic Effects of Copy Number Variants in Isolated Hypogonadotropic Hypogonadism.The Journal of clinical endocrinology and metabolism · 2022Article
- Reversible hypogonadotropic hypogonadism in men with the fertile eunuch/Pasqualini syndrome: A single-center natural history study.Frontiers in endocrinology · 2022Article
- Genetic architecture of self-limited delayed puberty and congenital hypogonadotropic hypogonadism.Frontiers in endocrinology · 2022Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
contextThe genetic architecture of isolated hypogonadotropic hypogonadism (IHH) has not been completely defined.
objectiveTo determine the role of copy number variants (CNVs) in IHH pathogenicity and define their phenotypic spectrum.
methodsExome sequencing (ES) data in IHH probands (n = 1394) (Kallmann syndrome [IHH with anosmia; KS], n = 706; normosmic IHH [nIHH], n = 688) and family members (n = 1092) at the Reproductive Endocrine Unit and the Center for Genomic Medicine of Massachusetts General Hospital were analyzed for CNVs and single nucleotide variants (SNVs)/indels in 62 known IHH genes. IHH subjects without SNVs/indels in known genes were considered "unsolved." Phenotypes associated with CNVs were evaluated through review of patient medical records. A total of 29 CNVs in 13 genes were detected (overall IHH cohort prevalence: ~2%). Almost all (28/29) CNVs occurred in unsolved IHH cases. While some genes (eg, ANOS1 and FGFR1) frequently harbor both CNVs and SNVs/indels, the mutational spectrum of others (eg, CHD7) was restricted to SNVs/indels. Syndromic phenotypes were seen in 83% and 63% of IHH subjects with multigenic and single gene CNVs, respectively.
conclusionCNVs in known genes contribute to ~2% of IHH pathogenesis. Predictably, multigenic contiguous CNVs resulted in syndromic phenotypes. Syndromic phenotypes resulting from single gene CNVs validate pleiotropy of some IHH genes. Genome sequencing approaches are now needed to identify novel genes and/or other elusive variants (eg, noncoding/complex structural variants) that may explain the remaining missing etiology of IHH.
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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.