Novel Compound Heterozygous Pathogenic Mutations of SLC5A5 in a Chinese Patient With Congenital Hypothyroidism
Background and ObjectivesDefects in the human sodium/iodide symporter (SLC5A5) gene have been reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify SLC5A5 mutations in Chinese patients with CH and to evaluate the function of the mutation.MethodsTwo hundred and seve...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-03-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.620117/full |
| _version_ | 1819119635815989248 |
|---|---|
| author | Cao-Xu Zhang Jun-Xiu Zhang Liu Yang Chang-Run Zhang Feng Cheng Rui-Jia Zhang Ya Fang Zheng Wang Feng-Yao Wu Pei-Zhang Li Jun Liang Rui Li Huai-Dong Song |
| author_facet | Cao-Xu Zhang Jun-Xiu Zhang Liu Yang Chang-Run Zhang Feng Cheng Rui-Jia Zhang Ya Fang Zheng Wang Feng-Yao Wu Pei-Zhang Li Jun Liang Rui Li Huai-Dong Song |
| author_sort | Cao-Xu Zhang |
| collection | DOAJ |
| description | Background and ObjectivesDefects in the human sodium/iodide symporter (SLC5A5) gene have been reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify SLC5A5 mutations in Chinese patients with CH and to evaluate the function of the mutation.MethodsTwo hundred and seventy-three patients with primary CH were screened for mutations in SLC5A5 using next-generation sequencing. We investigated the expression and cellular localization of the novel compound heterozygous mutation in SLC5A5. The functional activity of the mutants was further examined in vitro.ResultsIn 273 patients with CH, two previously undescribed pathogenic mutations p.Gly51AlafsTer45 (G51fs) and p.Gly421Arg (G421R) in a compound heterozygous state in SLC5A5 were identified in a pediatric patient. G51fs was located in the first intercellular loop connecting transmembrane segment I and II, whereas G421R was in the transmembrane segment (TMS) XI. G51fs and G421R resulted in a truncated NIS and reduced protein expression, respectively. In vitro experiments further showed that the normal function of iodine transport of sodium-iodide symporter (NIS) mutants was markedly impaired.ConclusionThe undescribed compound heterozygous mutation of SLC5A5 was discovered in a Chinese CH patient. The mutation led to significantly reduced NIS expression and impaired iodide transport function accompanied by the impaired location of the NIS on the plasma membrane. Our study thus provides further insights into the roles of SLC5A5 in CH pathogenesis. |
| first_indexed | 2024-12-22T06:07:55Z |
| format | Article |
| id | doaj.art-fd9b51c6039d4badbf51eec0267b1038 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-22T06:07:55Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-fd9b51c6039d4badbf51eec0267b10382022-12-21T18:36:21ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-03-011210.3389/fendo.2021.620117620117Novel Compound Heterozygous Pathogenic Mutations of SLC5A5 in a Chinese Patient With Congenital HypothyroidismCao-Xu Zhang0Jun-Xiu Zhang1Liu Yang2Chang-Run Zhang3Feng Cheng4Rui-Jia Zhang5Ya Fang6Zheng Wang7Feng-Yao Wu8Pei-Zhang Li9Jun Liang10Rui Li11Huai-Dong Song12The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Endocrinology, Maternal and Child Health Institute of Bozhou, Bozhou, ChinaThe Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Laboratory Medicine, Fujian Children’s Hospital, Fujian Provincial Maternity and Children’s Hospital, Fuzhou, ChinaThe Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Endocrinology, The Central Hospital of Xuzhou Affiliated to Xuzhou Medical College, Xuzhou, ChinaThe Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackground and ObjectivesDefects in the human sodium/iodide symporter (SLC5A5) gene have been reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify SLC5A5 mutations in Chinese patients with CH and to evaluate the function of the mutation.MethodsTwo hundred and seventy-three patients with primary CH were screened for mutations in SLC5A5 using next-generation sequencing. We investigated the expression and cellular localization of the novel compound heterozygous mutation in SLC5A5. The functional activity of the mutants was further examined in vitro.ResultsIn 273 patients with CH, two previously undescribed pathogenic mutations p.Gly51AlafsTer45 (G51fs) and p.Gly421Arg (G421R) in a compound heterozygous state in SLC5A5 were identified in a pediatric patient. G51fs was located in the first intercellular loop connecting transmembrane segment I and II, whereas G421R was in the transmembrane segment (TMS) XI. G51fs and G421R resulted in a truncated NIS and reduced protein expression, respectively. In vitro experiments further showed that the normal function of iodine transport of sodium-iodide symporter (NIS) mutants was markedly impaired.ConclusionThe undescribed compound heterozygous mutation of SLC5A5 was discovered in a Chinese CH patient. The mutation led to significantly reduced NIS expression and impaired iodide transport function accompanied by the impaired location of the NIS on the plasma membrane. Our study thus provides further insights into the roles of SLC5A5 in CH pathogenesis.https://www.frontiersin.org/articles/10.3389/fendo.2021.620117/fulliodine transportmutationSLC5A5next-generation sequencingcongenital hypothyroidism |
| spellingShingle | Cao-Xu Zhang Jun-Xiu Zhang Liu Yang Chang-Run Zhang Feng Cheng Rui-Jia Zhang Ya Fang Zheng Wang Feng-Yao Wu Pei-Zhang Li Jun Liang Rui Li Huai-Dong Song Novel Compound Heterozygous Pathogenic Mutations of SLC5A5 in a Chinese Patient With Congenital Hypothyroidism Frontiers in Endocrinology iodine transport mutation SLC5A5 next-generation sequencing congenital hypothyroidism |
| title | Novel Compound Heterozygous Pathogenic Mutations of SLC5A5 in a Chinese Patient With Congenital Hypothyroidism |
| title_full | Novel Compound Heterozygous Pathogenic Mutations of SLC5A5 in a Chinese Patient With Congenital Hypothyroidism |
| title_fullStr | Novel Compound Heterozygous Pathogenic Mutations of SLC5A5 in a Chinese Patient With Congenital Hypothyroidism |
| title_full_unstemmed | Novel Compound Heterozygous Pathogenic Mutations of SLC5A5 in a Chinese Patient With Congenital Hypothyroidism |
| title_short | Novel Compound Heterozygous Pathogenic Mutations of SLC5A5 in a Chinese Patient With Congenital Hypothyroidism |
| title_sort | novel compound heterozygous pathogenic mutations of slc5a5 in a chinese patient with congenital hypothyroidism |
| topic | iodine transport mutation SLC5A5 next-generation sequencing congenital hypothyroidism |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.620117/full |
| work_keys_str_mv | AT caoxuzhang novelcompoundheterozygouspathogenicmutationsofslc5a5inachinesepatientwithcongenitalhypothyroidism AT junxiuzhang novelcompoundheterozygouspathogenicmutationsofslc5a5inachinesepatientwithcongenitalhypothyroidism AT liuyang novelcompoundheterozygouspathogenicmutationsofslc5a5inachinesepatientwithcongenitalhypothyroidism AT changrunzhang novelcompoundheterozygouspathogenicmutationsofslc5a5inachinesepatientwithcongenitalhypothyroidism AT fengcheng novelcompoundheterozygouspathogenicmutationsofslc5a5inachinesepatientwithcongenitalhypothyroidism AT ruijiazhang novelcompoundheterozygouspathogenicmutationsofslc5a5inachinesepatientwithcongenitalhypothyroidism AT yafang novelcompoundheterozygouspathogenicmutationsofslc5a5inachinesepatientwithcongenitalhypothyroidism AT zhengwang novelcompoundheterozygouspathogenicmutationsofslc5a5inachinesepatientwithcongenitalhypothyroidism AT fengyaowu novelcompoundheterozygouspathogenicmutationsofslc5a5inachinesepatientwithcongenitalhypothyroidism AT peizhangli novelcompoundheterozygouspathogenicmutationsofslc5a5inachinesepatientwithcongenitalhypothyroidism AT junliang novelcompoundheterozygouspathogenicmutationsofslc5a5inachinesepatientwithcongenitalhypothyroidism AT ruili novelcompoundheterozygouspathogenicmutationsofslc5a5inachinesepatientwithcongenitalhypothyroidism AT huaidongsong novelcompoundheterozygouspathogenicmutationsofslc5a5inachinesepatientwithcongenitalhypothyroidism |