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. 2024 Jul;85(1):444-453.
doi: 10.1007/s12020-023-03581-7. Epub 2023 Nov 8.

Exome sequencing (ES) of a pediatric cohort with chronic endocrine diseases: a single-center study (within the framework of the TRANSLATE-NAMSE project)

Sebastian Gippert #  1 , Matias Wagner #  2   3 , Theresa Brunet  2   4 , Riccardo Berruti  2 , Melanie Brugger  2 , Eva M C Schwaibold  5 , Tobias B Haack  6 , Georg F Hoffmann  1 , Markus Bettendorf  1 , Daniela Choukair  7
Affiliations

Exome sequencing (ES) of a pediatric cohort with chronic endocrine diseases: a single-center study (within the framework of the TRANSLATE-NAMSE project)

Sebastian Gippert et al. Endocrine. 2024 Jul.

Abstract

Background: Endocrine disorders are heterogeneous and include a significant number of rare monogenic diseases.

Methods: We performed exome sequencing (ES) in 106 children recruited from a single center within the TRANSLATE‑NAMSE project. They were categorized into subgroups: proportionate short stature (PSS), disproportionate short stature (DSS), hypopituitarism (H), differences in sexual development (DSD), syndromic diseases (SD) and others.

Results: The overall diagnostic yield was 34.9% (n = 37/106), including 5 patients with variants in candidate genes, which have contributed to collaborations to identify gene-disease associations. The diagnostic yield varied significantly between subgroups: PSS: 16.6% (1/6); DSS: 18.8% (3/16); H: 17.1% (6/35); DSD: 37.5% (3/8); SD: 66.6% (22/33); others: 25% (2/8). Confirmed diagnoses included 75% ultrarare diseases. Three patients harbored more than one disease-causing variant, resulting in dual diagnoses.

Conclusions: ES is an effective tool for genetic diagnosis in pediatric patients with complex endocrine diseases. An accurate phenotypic description, including comprehensive endocrine diagnostics, as well as the evaluation of variants in multidisciplinary case conferences involving geneticists, are necessary for personalized diagnostic care. Here, we illustrate the broad spectrum of genetic endocrinopathies that have led to the initiation of specific treatment, surveillance, and family counseling.

Keywords: Exome sequencing; TRANSLATE-NAMSE; chronic pediatric endocrine diseases; multidisciplinary case conferences; rare diseases.

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Conflict of interest statement

The authors have no competing interests.

Figures

Fig. 1
Fig. 1
Variant classification of 106 patients with endocrine disorders. The bars show the distribution of variants according to the diagnoses. VUS variant of unknown significance, DSD disorder of sexual development; n = patients
Fig. 2
Fig. 2
Distribution of all disease-causing variants based on the mode of inheritance, with de novo variants representing the most common mode of inheritance
See this image and copyright information in PMC

References

    1. Shlomo M., Auchus R.J., Goldfine A.B., Koenig R.J., Rosen C.J. Williams textbook of endocrinology. Philadelphia: Elsevier; 2020.
    1. Bundesausschuss IbG: TRANSLATE-NAMSE – Verbesserung der Versorgung von Menschen mit seltenen Erkrankungen durch Umsetzung von im nationalen Aktionsplan (NAMSE) konsentierten Maßnahmen. https://innovationsfonds.g-ba.de/projekte/neue-versorgungsformen/transla... (2017). Accessed 20.01.2023.
    1. Kohler S, Gargano M, Matentzoglu N, Carmody LC, Lewis-Smith D, Vasilevsky NA, et al. The human phenotype ontology in 2021. Nucleic Acids Res. 2021;49(D1):D1207–D1217. doi: 10.1093/nar/gkaa1043. - DOI - PMC - PubMed
    1. Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) Genet Med. 2020;22(2):245–257. doi: 10.1038/s41436-019-0686-8. - DOI - PMC - PubMed
    1. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–424. doi: 10.1038/gim.2015.30. - DOI - PMC - PubMed

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