Submission Details

TUBGCP6 was first reported in relation to autosomal recessive microcephaly and chorioretinopathy 1 in 2012 (Puffenberger et al., 2012; PMID: 22279524). An important note is that this condition, which has both microcephaly and the ophthalmic/retinal phenotype, is distinct from simple microcephaly. No pre-curation was necessary for the gene as there is only one gene disease assertion for autosomal recessive microcephaly and chorioretinopathy 1 (OMIM: # 251270). 12 variants (missense, in-frame duplication, read-through, splice site, frameshift, and nonsense) that have been reported in 7 probands in 3 publications (PMIDs: 22279524, 25344692, 37031378) are included in this curation. The maximum score for genetic evidence has been reached. There is only one reported prenatal diagnosis of this condition, described by Thomas-Wilson et al., 2023 (PMID: 37031378), and found by fetal ultrasound/MRI exams showing microcephaly. The mechanism of pathogenicity is reported to be loss of function. This gene-disease relationship is also supported by experimental evidence (expression evidence, biochemical function, functional alteration; PMIDs: 19861490, 31874114). The deletion of the gene has been shown to cause cell division defects, consistent with short stature/developmental issues, often seen in affected individuals. In summary, there is definitive evidence supporting the relationship between TUBGCP6 and autosomal recessive chorioretinopathy and microcephaly 1. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Prenatal GCEP on the meeting date [May 31, 2023] (SOP Version 1).