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Split hand-foot malformation (MONDO:0016576) is characterized by median clefts of the central rays of hands and/or feet resulting in ectrodactyly (HP:0100257). A single male patient was reported with SHFM, tetralogy of Fallot (HP:0001636) and an Angelman-like phenotype who harbored a de novo 0.99 Mb deletion of chromosome 19p13.11 disrupting EPS15L1 (PMID:19353584). No additional EPS15L1 rearrangements were found in 21 other SHFM patients screened by MLPA.
The association of EPS15L1 disruption with SHFM is supported by this solitary de novo case; there is no report of familial segregation, point mutations, or functional studies directly implicating EPS15L1 in limb development. Given the absence of confirmatory genetic or in vivo functional data, current evidence is insufficient to establish EPS15L1 as a definitive SHFM gene.
Key Take-home: EPS15L1 may contribute to SHFM as part of a contiguous gene deletion, but further genetic and mechanistic studies are required to confirm its pathogenic role.
Gene–Disease AssociationLimitedSingle proband with de novo EPS15L1 deletion; no additional cases Genetic EvidenceLimitedOne individual with de novo EPS15L1 deletion; no familial segregation or point mutations Functional EvidenceNo reported evidenceNo functional studies specific to EPS15L1 in limb development |