IL11RA was first reported in relation to autosomal recessive craniosynostosis and dental anomalies (CRSDA) in 2011 by Nieminen et al. (PMID: 21741611). Fifteen variants (missense, duplications, nonsense) that have been reported in over 15 probands in two publications (PMIDs: 21741611, 24498618) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is reported to be loss of function. This gene-disease association is also supported by experimental evidence (mice models, cell cultures, and expression level evidence; PMID: 21741611). Mice models and cell cultures with mutated/homozygous null Il11ra exhibit the phenotype of craniosynostosis with dental anomalies, and the gene has been shown to be expressed in areas of interest in mice. In summary, IL11RA is definitively associated with autosomal recessive craniosynostosis with dental anomalies (CRSDA). 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 Craniomalformations GCEP on the meeting date 4/20/2023 (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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