Next-Generation Sequencing Analysis Reveals Frequent Familial Origin and Oligogenism in Congenital Hypothyroidism With Dyshormonogenesis
ContextCongenital 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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-06-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.657913/full |
| _version_ | 1818407442864668672 |
|---|---|
| author | Isabelle Oliver-Petit Thomas Edouard Thomas Edouard Virginie Jacques Virginie Jacques Marie Bournez Audrey Cartault Solange Grunenwald Frédérique Savagner Frédérique Savagner |
| author_facet | Isabelle Oliver-Petit Thomas Edouard Thomas Edouard Virginie Jacques Virginie Jacques Marie Bournez Audrey Cartault Solange Grunenwald Frédérique Savagner Frédérique Savagner |
| author_sort | Isabelle Oliver-Petit |
| collection | DOAJ |
| description | ContextCongenital 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.ObjectiveWe explored 19 candidate genes known to be causative for permanent or transient CH to evaluate the role of complex gene variations in CH phenotype.Patients, Design and SettingUsing the NGS approach, we studied 65 newborns with thyroid dyshormonogenesis (TDH). New variants were assessed in silico for pathogenicity.ResultsAmong 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 TG, DUOX2, TPO, or SLC5A5 genes in 10 infants and heterozygous variants in DUOX2, TG, TPO, and TSHR in 19 others. In seven cases, a heterozygous variant in the TG gene was the unique anomaly detected, but related to disturbed hormonal balance. Oligogenic variants were found in eight infants associated with severe CH and goiter in five of them.ConclusionThe 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. |
| first_indexed | 2024-12-14T09:27:55Z |
| format | Article |
| id | doaj.art-c52b1222859e47728c30e402f56cb326 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-14T09:27:55Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-c52b1222859e47728c30e402f56cb3262022-12-21T23:08:09ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-06-011210.3389/fendo.2021.657913657913Next-Generation Sequencing Analysis Reveals Frequent Familial Origin and Oligogenism in Congenital Hypothyroidism With DyshormonogenesisIsabelle Oliver-Petit0Thomas Edouard1Thomas Edouard2Virginie Jacques3Virginie Jacques4Marie Bournez5Audrey Cartault6Solange Grunenwald7Frédérique Savagner8Frédérique Savagner9Endocrine, Genetics, Bone Diseases, and Paediatric Gynecology Unit, Children’s Hospital, CHU Toulouse, Toulouse, FranceEndocrine, Genetics, Bone Diseases, and Paediatric Gynecology Unit, Children’s Hospital, CHU Toulouse, Toulouse, FranceInserm UMR 1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, FranceInserm UMR 1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, FranceBiochemistry and Genetic Laboratory, Federative Institute of Biology, CHU Toulouse, Toulouse, FrancePediatric Unit, Hospital Le Bocage, CHU Dijon, Dijon, FranceEndocrine, Genetics, Bone Diseases, and Paediatric Gynecology Unit, Children’s Hospital, CHU Toulouse, Toulouse, FranceDepartment of Endocrinology and Metabolic Diseases, Cardio-Vascular and Metabolic Unit, CHU Larrey, Toulouse, FranceInserm UMR 1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, FranceBiochemistry and Genetic Laboratory, Federative Institute of Biology, CHU Toulouse, Toulouse, FranceContextCongenital 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.ObjectiveWe explored 19 candidate genes known to be causative for permanent or transient CH to evaluate the role of complex gene variations in CH phenotype.Patients, Design and SettingUsing the NGS approach, we studied 65 newborns with thyroid dyshormonogenesis (TDH). New variants were assessed in silico for pathogenicity.ResultsAmong 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 TG, DUOX2, TPO, or SLC5A5 genes in 10 infants and heterozygous variants in DUOX2, TG, TPO, and TSHR in 19 others. In seven cases, a heterozygous variant in the TG gene was the unique anomaly detected, but related to disturbed hormonal balance. Oligogenic variants were found in eight infants associated with severe CH and goiter in five of them.ConclusionThe 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.https://www.frontiersin.org/articles/10.3389/fendo.2021.657913/fullhigh throughput molecular screeningfamilial originoligogenicitycongenital hypothyroidismthyroid dyshormonogenesis |
| spellingShingle | Isabelle Oliver-Petit Thomas Edouard Thomas Edouard Virginie Jacques Virginie Jacques Marie Bournez Audrey Cartault Solange Grunenwald Frédérique Savagner Frédérique Savagner Next-Generation Sequencing Analysis Reveals Frequent Familial Origin and Oligogenism in Congenital Hypothyroidism With Dyshormonogenesis Frontiers in Endocrinology high throughput molecular screening familial origin oligogenicity congenital hypothyroidism thyroid dyshormonogenesis |
| title | Next-Generation Sequencing Analysis Reveals Frequent Familial Origin and Oligogenism in Congenital Hypothyroidism With Dyshormonogenesis |
| title_full | Next-Generation Sequencing Analysis Reveals Frequent Familial Origin and Oligogenism in Congenital Hypothyroidism With Dyshormonogenesis |
| title_fullStr | Next-Generation Sequencing Analysis Reveals Frequent Familial Origin and Oligogenism in Congenital Hypothyroidism With Dyshormonogenesis |
| title_full_unstemmed | Next-Generation Sequencing Analysis Reveals Frequent Familial Origin and Oligogenism in Congenital Hypothyroidism With Dyshormonogenesis |
| title_short | Next-Generation Sequencing Analysis Reveals Frequent Familial Origin and Oligogenism in Congenital Hypothyroidism With Dyshormonogenesis |
| title_sort | next generation sequencing analysis reveals frequent familial origin and oligogenism in congenital hypothyroidism with dyshormonogenesis |
| topic | high throughput molecular screening familial origin oligogenicity congenital hypothyroidism thyroid dyshormonogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.657913/full |
| work_keys_str_mv | AT isabelleoliverpetit nextgenerationsequencinganalysisrevealsfrequentfamilialoriginandoligogenismincongenitalhypothyroidismwithdyshormonogenesis AT thomasedouard nextgenerationsequencinganalysisrevealsfrequentfamilialoriginandoligogenismincongenitalhypothyroidismwithdyshormonogenesis AT thomasedouard nextgenerationsequencinganalysisrevealsfrequentfamilialoriginandoligogenismincongenitalhypothyroidismwithdyshormonogenesis AT virginiejacques nextgenerationsequencinganalysisrevealsfrequentfamilialoriginandoligogenismincongenitalhypothyroidismwithdyshormonogenesis AT virginiejacques nextgenerationsequencinganalysisrevealsfrequentfamilialoriginandoligogenismincongenitalhypothyroidismwithdyshormonogenesis AT mariebournez nextgenerationsequencinganalysisrevealsfrequentfamilialoriginandoligogenismincongenitalhypothyroidismwithdyshormonogenesis AT audreycartault nextgenerationsequencinganalysisrevealsfrequentfamilialoriginandoligogenismincongenitalhypothyroidismwithdyshormonogenesis AT solangegrunenwald nextgenerationsequencinganalysisrevealsfrequentfamilialoriginandoligogenismincongenitalhypothyroidismwithdyshormonogenesis AT frederiquesavagner nextgenerationsequencinganalysisrevealsfrequentfamilialoriginandoligogenismincongenitalhypothyroidismwithdyshormonogenesis AT frederiquesavagner nextgenerationsequencinganalysisrevealsfrequentfamilialoriginandoligogenismincongenitalhypothyroidismwithdyshormonogenesis |