Homozygous deletion in TUSC3 causing syndromic intellectual disability: A new patient


  • Conflict of interest: none.

Correspondence to:

Agatino Battaglia, M.D., Stella Maris Clinical Research Institute for Child and Adolescent Neuropsychiatry, via dei Giacinti, 2—56128, Calambrone, Pisa, Italy.

E-mail: agatino.battaglia@inpe.unipi.it


Defects in the TUSC3 gene have been identified in individuals with nonsyndromic autosomal recessive intellectual disability (ARID), due to either point mutations or intragenic deletions. We report on a boy with a homozygous microdeletion 8p22, sizing 203 kb, encompassing the first exon of the TUSC3 gene, detected by SNP-array analysis (Human Gene Chip 6.0; Affymetrix). Both nonconsanguineous parents come from a small Sicilian village and were heterozygous carriers of the microdeletion. The propositus had a few dysmorphic features and a moderate cognitive impairment. Verbal communication was impaired, with an inappropriate phonetic inventory, important phono-articolatory distortions, and bucco-phonatory dyspraxia. Comprehension was possible for simple sentences. Behavior was characterized by motor instability, high tendency to irritability and distraibility, anxiety traits, and an oppositional-defiant disorder. His parents were of normal intelligence. TUSC3 is thought to encode a subunit of the endoplasmic reticulum-bound oligosaccharyltranferase complex that catalyzes a pivotal step in the protein N-glycosylation process. TUSC3 has been recently reported as a member of the plasma membrane Mg2+ transport system, with a possible involvement in learning abilities, working memory and short- and long-term memory. This is the third family in which a deletion has been described. Although the pathogenic mechanism has not been clarified yet, our report argues for a more prominent role of TUSC3 in the etiology of intellectual disability and that deletions encompassing this gene could be more common than expected. © 2013 Wiley Periodicals, Inc.