TG Gene Mutations and Congenital Hypothyroidism

June 25, 2007 updated by: University of Sao Paulo

Congenital Hypothyroidism Due to Thyroglobulin Mutations in an Inbred Brazilian Family: A Novel Compound Heterozygous Constellation and Intronic Mutation Related to Fetal Goiter.

The aim of this study was to identify mutations in the thyroglobulin gene that might be present in patients with fetal goiter and congenital goiter hypothyroidism.

Study Overview

Status

Completed

Conditions

Detailed Description

Congenital goitrous hypothyroid is commonly linked to thyroglobulin (TG) gene mutations.We aim to identify mutations in the TG gene that might be present in patients with fetal goiter and congenital goiter hypothyroidism.Four related patients with congenital goiter hypothyroidism from an inbred family were studied.Recombinant human TSH stimulation test, DNA sequencing and protein computer analysis were performed.We identified a novel compound heterozygous constellation (IVS30+1G>T/A2215D) in two siblings. It was also identified a homozygous intronic mutation (IVS30+1G>T) in their cousins, one of them with fetal goiter. The mutation IVS30+1G>T promotes an aberrant splicing and loss of the entire exon 30 (138 nt) in the resulting messenger RNA. The recent described mutation A2215D is located in the ACHE-like domain, which functions as a dimerization domain, facilitating efficient intracellular transport of the protein. Protein computer analysis suggested that the A2215D mutation causes TG structural alterations.A novel compound heterozygous constellation (IVS30+1G>T/A2215D) and the previously described mutation (IVS30+1G>T) that cause severe congenital hypothyroidism due to defective TG synthesis have been identified. The mutation IVS30+1G>T may be related to fetal goiter and hypothyroidism due to TG instability and impaired TG export to the colloid. This study shows the efficiency of the use of rhTSH in the differential diagnosis of CH due to TG defective synthesis and the importance of molecular diagnosis of CH for possible intrauterine treatment, thereby avoiding damage to the neuropsychomotor system.

Study Type

Observational

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with congenital hypothyroidism due to thyroglobulin defective synthesis.

Exclusion Criteria:

  • Patients with another disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo

Collaborators

Fundação de Amparo à Pesquisa do Estado de São Paulo

Investigators

  • Principal Investigator: Viviane Pardo, University of Sao Paulo
  • Study Director: Geraldo Medeiros-Neto, University of Sao Paulo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2003

Study Completion (ACTUAL)

June 1, 2007

Study Registration Dates

First Submitted

June 25, 2007

First Submitted That Met QC Criteria

June 25, 2007

First Posted (ESTIMATE)

June 27, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

June 27, 2007

Last Update Submitted That Met QC Criteria

June 25, 2007

Last Verified

June 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRN989/03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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