TSH Receptor Mutations Among a Consanguineous Community (TSHR)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
HaEmek Medical Center, Israel
ClinicalTrials.gov Identifier:
NCT00747760
First received: September 4, 2008
Last updated: September 10, 2008
Last verified: September 2008

September 4, 2008
September 10, 2008
December 2005
July 2006   (final data collection date for primary outcome measure)
Two specific TSHR mutations [ Time Frame: Finished ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00747760 on ClinicalTrials.gov Archive Site
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TSH Receptor Mutations Among a Consanguineous Community
The Prevalence of TSH Receptor Mutation Among the Arab Population of Israel

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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
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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)

Non-Probability Sample

Subjects belonging to extended family of the index case

Hypothyroidism
Not Provided
  • 1
    Extended family members
  • 2
    Control- subjects from the same town without known thyroid diseases
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
209
December 2006
July 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Subjects belonging to extended family of the index case

Exclusion Criteria:

Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
Israel,   United States
 
NCT00747760
920050194, 066-2005
No
Dr Yardena Tenenbaum-Rakover, Director Pediatric Endocrine Unit, Ha'Emek Medical Center, Afula, Israel
HaEmek Medical Center, Israel
National Institutes of Health (NIH)
Principal Investigator: Yardena Tenenbaum-Rakover, MD Ha'Emelk Medical Center,Afula, Israel
Principal Investigator: Samuel Refetoff, MD The University of Chicago, Chicago, Il, USA
HaEmek Medical Center, Israel
September 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP