Functional characterization of novel compound heterozygous missense SLC5A5 gene variants causing congenital dyshormonogenic hypothyroidism
2024

New Genetic Variants Linked to Congenital Hypothyroidism

Sample size: 1 publication 10 minutes Evidence: moderate

Author Information

Author(s): Carro Gerardo Hernán, Martín Mariano, Savy Sofía, Peyret Victoria, Geysels Romina Celeste, Montes Francisco Andrés, Bernal Barquero Carlos Eduardo, Ricci Valentina, Masnata María Eugenia, Masini-Repiso Ana María, Papendieck Patricia, Tellechea Mariana Lorena, Chiesa Ana Elena, Nicola Juan Pablo

Primary Institution: Universidad Nacional de Córdoba, Córdoba, Argentina

Hypothesis

Can novel pathogenic SLC5A5 gene variants be identified and functionally characterized in a patient with congenital dyshormonogenic hypothyroidism?

Conclusion

The study identifies novel compound heterozygous missense SLC5A5 gene variants that cause defective iodide accumulation, leading to congenital dyshormonogenic hypothyroidism.

Supporting Evidence

  • The study identified a novel pair of compound heterozygous missense variants in the SLC5A5 gene.
  • The p.G543R variant has been previously associated with congenital hypothyroidism.
  • The novel p.L562M variant was not reported in the Genome Aggregation Consortium dataset.
  • Functional studies showed that the p.L562M variant reduces iodide accumulation due to defective expression of the mutant NIS protein.

Takeaway

This study found new genetic changes in a patient that prevent their body from properly using iodide, which is important for making thyroid hormones.

Methodology

Whole-exome sequencing was used to identify gene variants, followed by in silico analysis and in vitro functional characterization.

Limitations

The study is based on a single patient, which may limit the generalizability of the findings.

Participant Demographics

The participant was a full-term female infant born to non-consanguineous Caucasian parents.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.3389/fendo.2024.1465176

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