Evidence map›Paper›PMID 40924640›Full record

ArticleNeuroendocrinology2026

Expanded Targeted-Exome Sequencing and Functional Validation Improve Molecular Diagnosis and Refine Genotype-Phenotype Correlations in Congenital Hypogonadotropic Hypogonadism.

Jessica Silva Fausto, Lucas G A Ferreira, Silvia R Correa-Silva, Maria Izabel Chiamolera, Elisa Napolitano E Ferreira, Ilda Kunii, Magnus R Dias-da-Silva

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In one paragraph

Article in Neuroendocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Jessica Silva FaustoLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Lucas G A FerreiraLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Silvia R Correa-SilvaLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil, silvia.correa@unifesp.br.
Maria Izabel ChiamoleraLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Elisa Napolitano E FerreiraResearch and Development, Fleury Group, São Paulo, Brazil.
Ilda KuniiLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Magnus R Dias-da-SilvaLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionCongenital hypogonadotropic hypogonadism (CHH) arises from defects in the synthesis, secretion, or action of gonadotropin-releasing hormone (GnRH), resulting in incomplete or absent pubertal development and various nonreproductive features. CHH is genetically heterogeneous, with over 50 genes implicated in its pathogenesis. This study aimed to elucidate the genetic variants of CHH in a cohort of patients from a single-center endocrinology unit.

methodsWe used a targeted next-generation sequencing panel to analyze 52 CHH-related genes in 35 patients. Functional studies validated two of the identified variants.

resultsMolecular etiology was identified in 20 of 35 (57%) patients. Among these, 12 (39%) had variants in multiple CHH-related genes, with oligogenic inheritance confirmed in two cases. Novel pathogenic variants (both single nucleotide variants and copy number variants) were identified, including ANOS1 p.Gln238* and c.318+2T>C, CHD7 p.Ser734Ilefs5 and p.Gln592Serfs16, FGFR1 p.Ala36Profs67, c.1663+5G>A, and p.Tyr210*, DMXL2 deletion (83.1 Kb), and SOX2 deletion (1.1 Mb). In total, 21 pathogenic or likely pathogenic variants across 15 CHH-related genes were detected, including ANOS1, CHD7, FGFR1, PROKR2, and others. A functional study confirmed the loss of function in the KISS1R p.Ala203Asp variant.

conclusionOur findings demonstrate the utility of a next-generation sequencing panel in diagnosing genetically complex conditions like CHH and underscore the role of oligogenic inheritance in its phenotypic diversity. The inclusion of genes previously associated with syndromic CHH forms such as CHARGE in the exome panel may highlight possible shared mechanisms with neurodevelopmental disorders, aiding early diagnosis, genetic counseling, and treatment.

Indexed as

Exome SequencingGenetic Association StudiesHypogonadismAdolescentAdultChildDNA-Binding ProteinsDNA HelicasesExtracellular Matrix ProteinsFemaleHigh-Throughput Nucleotide SequencingHumansMaleNerve Tissue ProteinsReceptor, Fibroblast Growth Factor, Type 1Young AdultANOS1 protein, humanCHD7 protein, humanDNA-Binding ProteinsDNA HelicasesExtracellular Matrix ProteinsFGFR1 protein, humanNerve Tissue ProteinsReceptor, Fibroblast Growth Factor, Type 1Congenital hypogonadotropic hypogonadismGenetic variantsKallmann syndromeKISS1RTargeted next-generation sequencing

Identifiers

PMID40924640
PMCPMC13322688

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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.