Genetic and Phenotypic Characteristics of Congenital Hypothyroidism in a Chinese Cohort
BackgroundThe molecular etiology and the genotype–phenotype correlation of congenital hypothyroidism (CH) remain unclear.MethodsWe performed genetic analysis in 42 newborns with CH using whole-exome sequencing. Patients were divided into a single-gene group and a multi-gene group according to the nu...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.705773/full |
| _version_ | 1818607990331146240 |
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| author | Wei Long Fang Guo Ruen Yao Ying Wang Huaiyan Wang Bin Yu Peng Xue |
| author_facet | Wei Long Fang Guo Ruen Yao Ying Wang Huaiyan Wang Bin Yu Peng Xue |
| author_sort | Wei Long |
| collection | DOAJ |
| description | BackgroundThe molecular etiology and the genotype–phenotype correlation of congenital hypothyroidism (CH) remain unclear.MethodsWe performed genetic analysis in 42 newborns with CH using whole-exome sequencing. Patients were divided into a single-gene group and a multi-gene group according to the number of affected genes, or divided into a monoallelic group, a biallelic group, and an oligogenic group according to the pattern of the detected variants. The clinical characteristics were compared between groups.ResultsThyroid dysgenesis (TD) was observed in 10 patients and goiter in 5 patients, whereas 27 patients had normal-sized gland-in-situ (GIS). We identified 58 variants in five genes in 29 patients. The genes with the most frequent variants were DUOX2 (70.7%), followed by TSHR (12.1%), DUOXA2 (10.3%), and TPO (5.2%). Variants in the genes causing dyshormonogenesis (DH) were more common than those in the genes causing TD (87.9% versus 12.1%). Among the patients with detected variants, 26 (89.7%) were harboring a single gene variant (single-gene group), which include 22 patients harboring biallelic variants (biallelic group) and four patients harboring monoallelic variants (monoallelic group). Three (10.3%) patients harbored variants in two or three genes (multi-gene group or oligogenic group). Compared with the single-gene group, the levothyroxine (L-T4) dose at 1 year of age was higher in the multi-gene group (p = 0.018). A controllable reduction in the L-T4 dose was observed in 25% of patients in the monoallelic group and 59.1% of patients in the biallelic group; however, no patients with such reduction in the L-T4 dose were observed in the oligogenic group.ConclusionsPatients with normal-sized GIS accounted for the majority of our cohort. Genetic defects in the genes causing DH were more common than those in the genes causing TD, with biallelic variants in DUOX2 being dominant. DH might be the leading pathophysiology of CH in Chinese individuals. |
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| language | English |
| last_indexed | 2024-12-16T14:35:31Z |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-b318f35991134b01bac839da56e3c7262022-12-21T22:28:07ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-09-011210.3389/fendo.2021.705773705773Genetic and Phenotypic Characteristics of Congenital Hypothyroidism in a Chinese CohortWei Long0Fang Guo1Ruen Yao2Ying Wang3Huaiyan Wang4Bin Yu5Peng Xue6Department of Medical Genetics, Affiliated Changzhou Maternal and Child Health Care Hospital, Nanjing Medical University, Changzhou, ChinaDepartment of Medical Genetics, Affiliated Changzhou Maternal and Child Health Care Hospital, Nanjing Medical University, Changzhou, ChinaDepartment of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Affiliated Changzhou Maternal and Child Health Care Hospital, Nanjing Medical University, Changzhou, ChinaDepartment of Pediatrics, Affiliated Changzhou Maternal and Child Health Care Hospital, Nanjing Medical University, Changzhou, ChinaDepartment of Medical Genetics, Affiliated Changzhou Maternal and Child Health Care Hospital, Nanjing Medical University, Changzhou, ChinaDepartment of Pediatrics, Affiliated Changzhou Children’s Hospital of Nantong University, Changzhou, ChinaBackgroundThe molecular etiology and the genotype–phenotype correlation of congenital hypothyroidism (CH) remain unclear.MethodsWe performed genetic analysis in 42 newborns with CH using whole-exome sequencing. Patients were divided into a single-gene group and a multi-gene group according to the number of affected genes, or divided into a monoallelic group, a biallelic group, and an oligogenic group according to the pattern of the detected variants. The clinical characteristics were compared between groups.ResultsThyroid dysgenesis (TD) was observed in 10 patients and goiter in 5 patients, whereas 27 patients had normal-sized gland-in-situ (GIS). We identified 58 variants in five genes in 29 patients. The genes with the most frequent variants were DUOX2 (70.7%), followed by TSHR (12.1%), DUOXA2 (10.3%), and TPO (5.2%). Variants in the genes causing dyshormonogenesis (DH) were more common than those in the genes causing TD (87.9% versus 12.1%). Among the patients with detected variants, 26 (89.7%) were harboring a single gene variant (single-gene group), which include 22 patients harboring biallelic variants (biallelic group) and four patients harboring monoallelic variants (monoallelic group). Three (10.3%) patients harbored variants in two or three genes (multi-gene group or oligogenic group). Compared with the single-gene group, the levothyroxine (L-T4) dose at 1 year of age was higher in the multi-gene group (p = 0.018). A controllable reduction in the L-T4 dose was observed in 25% of patients in the monoallelic group and 59.1% of patients in the biallelic group; however, no patients with such reduction in the L-T4 dose were observed in the oligogenic group.ConclusionsPatients with normal-sized GIS accounted for the majority of our cohort. Genetic defects in the genes causing DH were more common than those in the genes causing TD, with biallelic variants in DUOX2 being dominant. DH might be the leading pathophysiology of CH in Chinese individuals.https://www.frontiersin.org/articles/10.3389/fendo.2021.705773/fullhypothyroidismwhole-exome sequencingbiallelic variantoligogenic variantcharacteristic |
| spellingShingle | Wei Long Fang Guo Ruen Yao Ying Wang Huaiyan Wang Bin Yu Peng Xue Genetic and Phenotypic Characteristics of Congenital Hypothyroidism in a Chinese Cohort Frontiers in Endocrinology hypothyroidism whole-exome sequencing biallelic variant oligogenic variant characteristic |
| title | Genetic and Phenotypic Characteristics of Congenital Hypothyroidism in a Chinese Cohort |
| title_full | Genetic and Phenotypic Characteristics of Congenital Hypothyroidism in a Chinese Cohort |
| title_fullStr | Genetic and Phenotypic Characteristics of Congenital Hypothyroidism in a Chinese Cohort |
| title_full_unstemmed | Genetic and Phenotypic Characteristics of Congenital Hypothyroidism in a Chinese Cohort |
| title_short | Genetic and Phenotypic Characteristics of Congenital Hypothyroidism in a Chinese Cohort |
| title_sort | genetic and phenotypic characteristics of congenital hypothyroidism in a chinese cohort |
| topic | hypothyroidism whole-exome sequencing biallelic variant oligogenic variant characteristic |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.705773/full |
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