title: 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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: 1 Laboratorio de Biología Molecular, Departamento de Genética, Instituto Nacional de Pediatría , Mexico City, Mexico.
authors.forename: Benilde
authors.initials: B
authors.lastname: García-de Teresa
authors.forename: Ariadna
authors.initials: A
authors.lastname: González-Del Angel
authors.forename: Miriam Erandi
authors.initials: ME
authors.lastname: Reyna-Fabián
authors.forename: María de la Luz
authors.initials: Mde L
authors.lastname: Ruiz-Reyes
authors.forename: Raúl
authors.initials: R
authors.lastname: Calzada-León
authors.forename: Bernardo
authors.initials: B
authors.lastname: Pérez-Enríquez
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Alcántara-Ortigoza
mesh_terms: D002675:Child, Preschool; D019295:Computational Biology; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007037:Hypothyroidism / Q000150:complications / Q000235:genetics; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D027501:Monocarboxylic Acid Transporters / Q000235:genetics*; D009123:Muscle Hypotonia / Q000235:genetics*; D009133:Muscular Atrophy / Q000235:genetics*; D010641:Phenotype; D027981:Symporters; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D027501:Monocarboxylic Acid Transporters; C090735:SLC16A2 protein, human; D027981:Symporters; D014284:Triiodothyronine; D013974:Thyroxine