Next-Generation Sequencing Analysis Reveals Frequent Familial Origin and Oligogenism in Congenital Hypothyroidism With Dyshormonogenesis.


Journal

Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782

Informations de publication

Date de publication:
2021
Historique:
received: 24 01 2021
accepted: 31 05 2021
entrez: 12 7 2021
pubmed: 13 7 2021
medline: 22 1 2022
Statut: epublish

Résumé

Congenital hypothyroidism (CH) is related to dyshormonogenesis in 15% to 40% of the world population and associated with homozygous or heterozygous variants in the main genes of the hormone synthesis pathway. Emerging diagnostic tools, such as next-generation sequencing (NGS), have been used to efficiently explore panels of genes and identify complex mechanisms of pathogenesis. We explored 19 candidate genes known to be causative for permanent or transient CH to evaluate the role of complex gene variations in CH phenotype. Using the NGS approach, we studied 65 newborns with thyroid dyshormonogenesis (TDH). New variants were assessed Among the 65 infants, 56.9% presented a variant in one or more genes of the thyroid hormone synthesis axis. We identified homozygous or compound heterozygous variants in the The systematic exploration of genes involved in thyroid hormone synthesis by NGS in TDH showed high diagnostic relevance. Oligogenic inheritance could be related to phenotypic heterogeneity and a high frequency of goiter.

Identifiants

pubmed: 34248839
doi: 10.3389/fendo.2021.657913
pmc: PMC8264654
doi:

Substances chimiques

Autoantigens 0
Iron-Binding Proteins 0
Receptors, Thyrotropin 0
Symporters 0
TSHR protein, human 0
sodium-iodide symporter 4XE5NDT4K1
Dual Oxidases EC 1.11.1.-
TPO protein, human EC 1.11.1.7
Iodide Peroxidase EC 1.11.1.8

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

657913

Informations de copyright

Copyright © 2021 Oliver-Petit, Edouard, Jacques, Bournez, Cartault, Grunenwald and Savagner.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Isabelle Oliver-Petit (I)

Endocrine, Genetics, Bone Diseases, and Paediatric Gynecology Unit, Children's Hospital, CHU Toulouse, Toulouse, France.

Thomas Edouard (T)

Endocrine, Genetics, Bone Diseases, and Paediatric Gynecology Unit, Children's Hospital, CHU Toulouse, Toulouse, France.
Inserm UMR 1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France.

Virginie Jacques (V)

Inserm UMR 1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France.
Biochemistry and Genetic Laboratory, Federative Institute of Biology, CHU Toulouse, Toulouse, France.

Marie Bournez (M)

Pediatric Unit, Hospital Le Bocage, CHU Dijon, Dijon, France.

Audrey Cartault (A)

Endocrine, Genetics, Bone Diseases, and Paediatric Gynecology Unit, Children's Hospital, CHU Toulouse, Toulouse, France.

Solange Grunenwald (S)

Department of Endocrinology and Metabolic Diseases, Cardio-Vascular and Metabolic Unit, CHU Larrey, Toulouse, France.

Frédérique Savagner (F)

Inserm UMR 1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France.
Biochemistry and Genetic Laboratory, Federative Institute of Biology, CHU Toulouse, Toulouse, France.

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Classifications MeSH