ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000007.13) (NC_000007.14)

Haploinsufficiency phenotype comments:

Non-focal heterozygous deletions and chromosomal rearrangements involving 7q21 have been reported in patients with Split-hand/foot malformation 1 (SHFM1). As all reported deletions involving DLX5 include additional genes, the potential haploinsufficiency for DLX5 alone is not known. The minimal deleted region in SHFM1 includes the closely linked gene, DLX 6, as well as the gene SHFM1 (formerly DSS1). Concomitant haploinsufficiency for DLX5 and DLX6 is currently favored as the pathogenic mechanism for SHFM1 [See PMIDs 22342398 and 19401716 and OMIM for reviews of the literature]. Supportive evidence includes a correlative spatiotemporal gene expression pattern of DLX5 and DLX6 and similar malformation phenotypes in a mouse DLX5/DLX6 double KO model. A 2012 study reported the first intragenic DLX5 mutation in a consanguineous family with an unusual SHFM1 phenotype, however this mutation was homozygous and its functional consequence has not yet been tested [PMID 22121204].

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity