Deletion of exon 1 of the SLC16A2 gene: a common occurrence in patients with Allan-Herndon-Dudley syndrome.

Abstract

BACKGROUND:

Allan-Herndon-Dudley syndrome (AHDS) is an X-linked type of mental retardation resulting from hindered thyroid hormone access to neurons. Clustered nonrecurrent deletions of SLC16A2 exon 1 have been described in three patients with AHDS. We report a fourth patient with such a deletion and discuss possible mechanisms leading to these rearrangements.

CASE PRESENTATION:

A three-and-a-half-year-old male with clinical and biochemical AHDS phenotype and a history of normal neonatal screening for hypothyroidism underwent SLC16A2 molecular analysis. Unexpectedly, he showed skeletal signs of hypothyroidism.

METHODS AND RESULTS:

The exons of the SLC16A2 (MCT8) gene and the sequences surrounding exon 1 were amplified using PCR. The patient had a 36-kb deletion affecting exon 1 of SLC16A2. The deletion junction was subjected to bioinformatic analyses, along with two other reported exon 1 deletion junctions, identifying possible sequence features and mechanisms responsible for such genomic rearrangements.

DISCUSSION/CONCLUSION:

This patient had a classic AHDS phenotype with an unexpectedly large anterior fontanel and delayed bone age and dentition. Bioinformatic analyses suggested that exon 1 deletions in patients with AHDS are caused by microhomology-mediated replicative-based and nonhomologous end-joining mechanisms. Rearrangement susceptibility may be due to the size of intron 1 and the percentage of repeat sequences.

• Authors: Benilde García-de Teresa, Ariadna González-Del Angel, Miriam Erandi Reyna-Fabián, María de la Luz Ruiz-Reyes, Raúl Calzada-León, Bernardo Pérez-Enríquez, Miguel Angel Alcántara-Ortigoza
• Journal: Thyroid : official journal of the American Thyroid Association (Thyroid) Vol. 25 Issue 3 Pg. 361-7 (Mar 2015) ISSN: 1557-9077 [Electronic] United States
• PMID: 25517855 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Monocarboxylic Acid Transporters
• SLC16A2 protein, human
• Symporters
• Triiodothyronine
• Thyroxine

Topics

• Child, Preschool
• Computational Biology
• Exons
• Female
• Gene Deletion
• Humans
• Hypothyroidism (complications, genetics)
• Male
• Mental Retardation, X-Linked (genetics)
• Monocarboxylic Acid Transporters (genetics)
• Muscle Hypotonia (genetics)
• Muscular Atrophy (genetics)
• Phenotype
• Symporters
• Thyroxine (blood)
• Triiodothyronine (blood)