Severe microcephaly
Gene: TRIOThe rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 10 Mar 2022, 1:37 p.m. | Last Modified: 10 Mar 2022, 1:37 p.m.
Panel Version: 2.292
Comment on list classification: New gene added by Zornitza Stark. There is sufficient evidence to promote this gene to Green status at the next GMS panel update - microcephaly of relevant severity to this panel is observed in at least 12 unrelated families with TRIO variants. Pathogenicity is supported by functional data and animal model.Created: 18 May 2021, 10:16 a.m. | Last Modified: 18 May 2021, 10:16 a.m.
Panel Version: 2.158
The nonsense mutations are spread along the TRIO sequence, and affected individuals show variable neurodevelopmental phenotypes. In contrast, missense variants cluster into two mutational hotspots in the TRIO sequence, one in the seventh spectrin repeat and one in the RAC1-activating GEFD1. Individuals with a pathogenic variant in the seventh spectrin repeat have a more severe ID associated with macrocephaly than do most individuals with GEFD1 variants, who display milder ID and microcephaly.
Sources: Expert listCreated: 4 Sep 2020, 10:31 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Mental retardation, autosomal dominant 44, MIM# 617061
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q2_21_rating was removed from gene: TRIO.
Source Expert Review Green was added to TRIO. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: trio has been classified as Amber List (Moderate Evidence).
Publications for gene: TRIO were set to 26721934; 32109419
Tag Q2_21_rating tag was added to gene: TRIO.
Phenotypes for gene: TRIO were changed from Mental retardation, autosomal dominant 44, MIM# 617061 to Intellectual developmental disorder, autosomal dominant 44, with microcephaly, OMIM:617061
gene: TRIO was added gene: TRIO was added to Severe microcephaly. Sources: Expert list Mode of inheritance for gene: TRIO was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRIO were set to 26721934; 32109419 Phenotypes for gene: TRIO were set to Mental retardation, autosomal dominant 44, MIM# 617061 Review for gene: TRIO was set to GREEN gene: TRIO was marked as current diagnostic