TSH Receptor Mutations Among a Consanguineous Community (TSHR)
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| First Received Date ICMJE | September 4, 2008 | ||||||||
| Last Updated Date | September 10, 2008 | ||||||||
| Start Date ICMJE | December 2005 | ||||||||
| Primary Completion Date | July 2006 (final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
Two specific TSHR mutations [ Time Frame: Finished ] [ Designated as safety issue: No ] | ||||||||
| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | Complete list of historical versions of study NCT00747760 on ClinicalTrials.gov Archive Site | ||||||||
| Current Secondary Outcome Measures ICMJE | Not Provided | ||||||||
| Original Secondary Outcome Measures ICMJE | Not Provided | ||||||||
| Current Other Outcome Measures ICMJE | Not Provided | ||||||||
| Original Other Outcome Measures ICMJE | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | TSH Receptor Mutations Among a Consanguineous Community | ||||||||
| Official Title ICMJE | The Prevalence of TSH Receptor Mutation Among the Arab Population of Israel | ||||||||
| Brief Summary | Resistance to thyrotropin (RTSH) is a condition of impaired responsiveness of the thyroid gland to TSH, characterized by elevated TSH, low or normal thyroid hormone levels, and hypoplastic or normal-sized thyroid gland. The aim of the present study was to evaluate the clinical course over time,the genotype-phenotype association and the frequency of two different TSH-receptor (TSHR) mutations in a highly consanguineous population of the town of Um-El-Fahem. |
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| Detailed Description | Resistance to thyrotropin (RTSH) is a syndrome involving reduced sensitivity to TSH. It is characterized by elevated TSH, absence of goiter (normal or hypoplastic thyroid gland) and normal to very low levels of thyroid hormones. The TSH-receptor (TSHR) gene is located on chromosome 14q31 and it consists of extracellular, trans-membrane and intracellular domains. Mutation in the TSHR may cause either gain or loss of function of the receptor. Loss-of-function mutations are autosomal-recessively inherited and lead to a spectrum of phenotypes, ranging from mild euthyroid hyperthyrotropinemia to severe congenital hypothyroidism (CH). Insensitivity to TSH depends on both the severity and location of the TSHR mutations. Since the first report of familial euthyroid hyperthyrotropinemia caused by a TSHR mutation, several cases of loss-of-function mutations of the TSHR have been reported however only a few reports on the outcome of patients affected with TSHR mutations. Whether the condition of euthyroid hyperthyrotropinemia leads to clinical hypothyroidism, remains stable or normalizes over time has yet to be elucidated. We recently described a unique novel TSHR-inactivating mutation located at the third extracellular loop that preferentially affected the inositol phosphate (IP) pathway in three sisters of Arab-Muslim decent that presented with euthyroid hyperthyrotropinemia. Further analysis of the extended family revealed additional members with TSHR syndrome phenotype carrying two different TSHR mutations. All the affected subjects live in the same town. The aim of the present study was to evaluate the clinical course over time, the genotype-phenotype association and the frequency of these two different TSHR mutations among the highly consanguineous population of the town of Um El Fahem. |
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| Study Type ICMJE | Observational | ||||||||
| Study Design ICMJE | Observational Model: Cohort Time Perspective: Prospective |
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| Target Follow-Up Duration | Not Provided | ||||||||
| Biospecimen | Retention: Samples With DNA Description: Blood samples were taken with EDTA and Genomic DNA was extracted from peripheral mononuclear cells using the Blood Amp Kit (QIAGEN Inc., Valencia, CA) |
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| Sampling Method | Non-Probability Sample | ||||||||
| Study Population | Subjects belonging to extended family of the index case |
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| Condition ICMJE | Hypothyroidism | ||||||||
| Intervention ICMJE | Not Provided | ||||||||
| Study Group/Cohort (s) |
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| Publications * | Grasberger H, Van Sande J, Hag-Dahood Mahameed A, Tenenbaum-Rakover Y, Refetoff S. A familial thyrotropin (TSH) receptor mutation provides in vivo evidence that the inositol phosphates/Ca2+ cascade mediates TSH action on thyroid hormone synthesis. J Clin Endocrinol Metab. 2007 Jul;92(7):2816-20. Epub 2007 Apr 24. | ||||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Completed | ||||||||
| Enrollment ICMJE | 209 | ||||||||
| Completion Date | December 2006 | ||||||||
| Primary Completion Date | July 2006 (final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria: |
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| Gender | Both | ||||||||
| Ages | Not Provided | ||||||||
| Accepts Healthy Volunteers | No | ||||||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||||
| Location Countries ICMJE | United States, Israel | ||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT00747760 | ||||||||
| Other Study ID Numbers ICMJE | 920050194, 066-2005 | ||||||||
| Has Data Monitoring Committee | No | ||||||||
| Responsible Party | Dr Yardena Tenenbaum-Rakover, Director Pediatric Endocrine Unit, Ha'Emek Medical Center, Afula, Israel | ||||||||
| Study Sponsor ICMJE | HaEmek Medical Center, Israel | ||||||||
| Collaborators ICMJE | National Institutes of Health (NIH) | ||||||||
| Investigators ICMJE |
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| Information Provided By | HaEmek Medical Center, Israel | ||||||||
| Verification Date | September 2008 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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