ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000005.9) (NC_000005.10)
Evidence for haploinsufficiency phenotype
PubMed ID Description
25533962 The 'Deciphering Developmental Disorders' (DDD) study (Nature, 2015) reported finding 2 patients with de novo missense and a patient with a de novo 82Kb deletion of 16 exons in the TRIO gene. The study used a combination of exome sequencing and array-based detection of chromosomal rearrangements and included 1,133 children with severe, undiagnosed developmental disorders and their parents.
25363760 De Rubeis et al. (2014) used exome sequencing and statistical analyses to identify autism associated genes. TRIO was identified as one such candidate gene as a result of a de novo loss of function mutation in one case (out of 3,871 autism cases).
26721934 Ba et al (2016) reported the detection of a de novo deletion of TRIO in a child with intellectual disability (ID). Three additional cases with truncating mutations were found by targeted sequencing of the TRIO gene in over 2300 patients with ID. The authors indicate that the data supports loss of TRIO function as causal for the clinical phenotype.

Haploinsufficiency phenotype comments:

Heterozygous mutations in TRIO are associated with Mental retardation, autosomal dominant 44. Most patients have mild craniofacial abnormalities, mild to borderline ID and behavioral problems. Although most variants reported to date are de novo and truncating, in at least one case, inheritance from a similarly affected parent has been reported (Varvagiannis et al., 2017).

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

No duplications involving only the entire TRIO gene reported