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This report describes a limited association between IL1RAPL2 (HGNC:5997) and Sotos syndrome (MONDO:0019349). A single case report identified an 862 kb deletion at Xq22.3 in a patient with Sotos syndrome features, including hyperextensible skin and joint hypermobility (PMID:21834033). The deletion encompassed several genes; among these, IL1RAPL2 was proposed as a candidate contributing to the severe developmental delay observed. However, segregation data are minimal with the deletion inherited from an unaffected mother, and no additional unrelated probands with point mutations or other lesions in IL1RAPL2 have been reported in association with Sotos syndrome.
The available genetic evidence is based solely on the presence of the deletion in an affected patient and lacks further functional validation specific to IL1RAPL2 in the Sotos syndrome context. Although IL1RAPL2 is biologically plausible given its expression and role in neurodevelopment, direct functional studies or corroborative case series have not been performed. This limitation underscores the need for cautious interpretation in the diagnostic setting, while also highlighting that additional evidence beyond current ClinGen scoring maximum might exist in broader genomic datasets.
Gene–Disease AssociationLimitedSingle case report with an 862 kb deletion including IL1RAPL2 (PMID:21834033) and limited familial segregation data. Genetic EvidenceLimitedEvidence stems from a chromosomal deletion encompassing IL1RAPL2 in one affected individual with no additional reported point mutations or functional variant data. Functional EvidenceLimitedNo direct functional studies on IL1RAPL2 in the context of Sotos syndrome have been reported; existing studies largely focus on related genes. |