**Note: In September 2021, the ClinGen Epilepsy GCEP opted to change the disease term on this curation from Undetermined Early-onset Epileptic Encephalopathy to Developmental and Epileptic Encephalopathy. The evidence summary below reflects this change. The original evidence and conclusion remains the same; therefore, the original date of approval has not been changed. **
A precuration for the ALG13 gene, performed by the Epilepsy Gene Curation Expert Panel, lead to the curation of ALG13 in association with X-linked Developmental and Epileptic Encephalopathy. The gene-disease association of ALG13 and X-linked Developmental and Epileptic Encephalopathy has been classified as Definitive. A p.Asn107Ser variant in ALG13 has been observed de novo in at least ten female probands, with onset of seizures within one to eight months of age. Additional maternally inherited missense variants in ALG13 have been reported in males with a variety of phenotypes, including seizures, bilateral optic nerve atrophy, and intellectual disability. One male individual (Timal et al. 2012, PMID 22492991) was reported to have an ALG13 missense variant and Congenital disorder of glycosylation, type 1, however no other papers besides Timal 2012 test for enzyme activity by way of serum transferrin isofocusing in males with ALG13 variants. One female proband with the de novo p.Asn107Ser variant was tested by transferrin isoform analysis and found to have normal results, indicating that the mechanism of disease is different between males and females (Dimassi et al. 2016; PMID 26138355). At this time no functional data exists to propose a mechanism of disease.
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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