TG Gene Mutations and Congenital Hypothyroidism

Congenital Hypothyroidism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00493103
• Other study ID #: PRN989/03
• Status: Completed
• Phase: N/A
• First received: June 25, 2007
• Last updated: June 25, 2007
• Start date: July 2003
• Est. completion date: June 2007

Study information

• Verified date: June 2007
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ministry of Health
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: June 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients with congenital hypothyroidism due to thyroglobulin defective synthesis.

Exclusion Criteria:

• Patients with another disease.

Study Design

Primary Purpose: Screening, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Congenital Hypothyroidism
• Hypothyroidism

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Fundação de Amparo à Pesquisa do Estado de São Paulo