ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

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Evidence for Loss Phenotypes

Evidence for loss of function 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.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.