AASS was first reported in relation to autosomal recessive hyperlysinemia in 2000 (Sacksteder KA, et al., 2000, PMID: 10775527). At least 13 unique variants (e.g. missense, nonsense, frameshift, large deletion, etc.) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 10 probands in 4 publications (PMIDs: 23890588, 10775527, 27604308, 23570448). Variants in this gene segregated with disease in 2 additional family members. Of note, this gene has also been implicated in Saccharopinuria but no putative causal variants have been identified in patients. This gene-disease relationship is supported by its biochemical function in lysine catabolism and a knock-in mouse model which recapitulates the human phenotype of hyperlysinemia (PMID: 35135854). In summary, AASS is definitively associated with autosomal recessive hyperlysinemia. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
This gene-disease pair was originally evaluated by the Aminoacidopathy GCEP on 06/29/2020. It was re-evaluated on 10/14/2022. As a result of this reevaluation, the classification increased from Moderate to Definitive with the addition of a new mouse model (PMIDs: 35135854).
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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