ArticleEuropean journal of human genetics : EJHG2018
Identification of variants in pleiotropic genes causing "isolated" premature ovarian insufficiency: implications for medical practice.
Article in European journal of human genetics : EJHG, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Pharmacogenomic studies of fertility outcomes in pediatric cancer survivors - A systematic review.Clinical and translational science · 2024Pooled it
- Mutation in MSH5 Causes Primary Ovarian Insufficiency and Successful Therapeutic Intervention by In Vitro Fertilisation.Journal of cellular and molecular medicine · 2026Article
- Adult-onset vanishing white matter disease due to a novel compound heterozygous EIF2B2 mutation: a case report and brief review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Defects in meiosis I contribute to the genesis of androgenetic hydatidiform moles.The Journal of clinical investigation · 2024Article
- Review
- A Human HomozygousGenes · 2024Article
- Primary ovarian insufficiency: update on clinical and genetic findings.Frontiers in endocrinology · 2024Review
- DNA double-strand break genetic variants in patients with premature ovarian insufficiency.Journal of ovarian research · 2023Review
- LARS2 variants can present as premature ovarian insufficiency in the absence of overt hearing loss.European journal of human genetics : EJHG · 2023Article
- Next-generation sequencing of 500 POI patients identified novel responsible monogenic and oligogenic variants.Journal of ovarian research · 2023Article
- Ovarian aging: mechanisms and intervention strategies.Medical review (2021) · 2022Review
- Premature Ovarian Insufficiency in CLPB Deficiency: Transcriptomic, Proteomic and Phenotypic Insights.The Journal of clinical endocrinology and metabolism · 2022Article
- Bilateral Ovarian Germ Cell Tumor in a 46,XX Female with Nijmegen Breakage Syndrome and Hypergonadotropic HypogonadismJournal of clinical research in pediatric endocrinology · 2022Article
- Article
- Whole-exome sequencing reveals new potential genes and variants in patients with premature ovarian insufficiency.Journal of assisted reproduction and genetics · 2022Article
- Targeted whole exome sequencing and Drosophila modelling to unveil the molecular basis of primary ovarian insufficiency.Human reproduction (Oxford, England) · 2021Article
- Compound heterozygous null mutations of NOBOX in sisters with delayed puberty and primary amenorrhea.Molecular genetics & genomic medicine · 2021Article
- Article
- Meiosis interrupted: the genetics of female infertility via meiotic failure.Reproduction (Cambridge, England) · 2021Review
- Isoform-Specific Roles of Mutant p63 in Human Diseases.Cancers · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Next-generation sequencing (NGS) is increasingly being used in a clinical setting for the molecular diagnosis of patients with heterogeneous disorders, such as premature ovarian insufficiency (POI). We performed NGS of ~1000 candidate genes in four unrelated patients with POI. We discovered the genetic cause of "isolated" POI in two cases, both of which had causative variants in surprising genes. In the first case, a homozygous nonsense variant in NBN was causative. Recessive function-altering NBN variants typically cause Nijmegen breakage syndrome characterized by microcephaly, cancer predisposition, and immunodeficiency, none of which are evident in the patient. At a cellular level, we found evidence of chromosomal instability. In the second case, compound heterozygous variants in EIF2B2 were causative. Recessive EIF2B2 function-altering variants usually cause leukoencephalopathy with episodic decline. Subsequent MRI revealed subclinical neurological abnormalities. These cases demonstrate that variants in NBN and EIF2B2, which usually cause severe syndromes, can cause apparently isolated POI, and that (1) NGS can precede clinical diagnosis and guide patient management, (2) NGS can redefine the phenotypic spectrum of syndromes, and (3) NGS may make unanticipated diagnoses that must be sensitively communicated to patients. Although there is rigorous debate about the handling of secondary/incidental findings using NGS, there is little discussion of the management of causative pleiotropic gene variants that have broader implications than that for which genetic studies were sought.
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