ROGDI was first reported in relation to autosomal recessive Amelocerebrohypohidrotic syndrome (Kohlschutter-Tonz syndrome) in 2012 (Schossig et al., PMID: 22424600). Kohlschutter-Tonz syndrome, originally described in Kohlschutter et al. (1974), (PMID: 4372200), is characterized by the presence of epilepsy, impaired intellectual development, and amelogenesis imperfecta. The mechanism of pathogenicity is known to be homozygous or compound heterozygous loss of function. All variants identified to date are expected to either cause premature mRNA degradation by NMD or dramatically alter the protein structure. Seven variants (3 nonsense, 3 splice site, and 1 frameshift) that have been reported in 12 probands in 4 publications (PMIDs: 22424600, 22482807,29153277,33866847) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. This gene-disease association is also supported by expression studies. (PMIDs: 22424600, 22482807). In summary, ROGDI is definitively associated with autosomal recessive Kohlschutter-Tonz syndrome. 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 Epilepsy GCEP on the meeting date 06/21/2022 (SOP Version 9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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