Severe microcephalyGene: TUBGCP2
Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - at least three families with distinct TUBGCP2 variants, presenting progressive severe microcephaly.
Created: 27 Aug 2020, 10:56 a.m. | Last Modified: 27 Aug 2020, 10:56 a.m.
Panel Version: 2.19
Associated with phenotype in OMIM, and a probable gene for Microcephaly and Lissencephaly Spectrum Disorders in G2P.
PMID: 31630790 (2019) - Five patients from four families with biallelic variants in the TUBGCP2 gene. Affected individuals shared phenotypic features that included progressive severe microcephaly (4/4, Z score: -4.0 to -9.0), developmental delay (5/5, mild-severe), seizures (4/5). All patients exhibited lissencephaly-spectrum phenotypes with varying degrees of cortical malformations on brain imaging including pachygyria and subcortical band heterotopia.
All variants segregated with disease in each family. Analysis of fibroblasts derived from one patient with a splice site variant revealed several abnormal transcripts, predicted to result in LoF. No further functional studies of other variants or patient cells were performed.
Created: 27 Aug 2020, 10:53 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, 618737
Gene: tubgcp2 has been classified as Amber List (Moderate Evidence).
gene: TUBGCP2 was added gene: TUBGCP2 was added to Severe microcephaly. Sources: Literature for-review tags were added to gene: TUBGCP2. Mode of inheritance for gene: TUBGCP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TUBGCP2 were set to 31630790 Phenotypes for gene: TUBGCP2 were set to Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, 618737 Review for gene: TUBGCP2 was set to GREEN