SPRED1 was first reported in relation to autosomal dominant Legius syndrome in 2007 (Brems et al., PMID 17704776). At least 63 variants (e.g. missense, in-frame indel, nonsense, frameshift) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. Variants in this gene have been reported in at least 21 probands in 2 publications (PMIDs: 17704776, 21089071). Variants in this gene segregated with disease in 35 additional family members. The mechanism for disease is haploinsufficiency as demonstrated by patient variants and experimental evidence (PMIDs: 17704776, 27313208, 27503857). This gene-disease association is supported by a mouse model, functional alteration studies investigating heterologously expressed patient variants and coimmunoprecipitation assays with NF1, BRAF and KRAS. In summary SPRED1 is definitively associated with autosomal dominant Legius syndrome.
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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