ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000016.9) (NC_000016.10)
  • Haploinsufficiency score: 3
  • Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
22308078 In this paper the authors describe a family with features of TBS in whom a novel 149kb deletion (chr16:49,625,560-49,802,988, hg18) spanning the SALL1 gene was identified by high resolution SNP microarray.
16429401 Reports three heterozygous deletions found in three families with features of TBS. In the first family, a 75 kb deletion including all SALL1 exons had been inherited by two siblings from their father. A second, sporadic patient carried a de novo 1.9-2.6Mb deletion including the whole SALL1 gene, and yet another sporadic case was found to carry an intragenic deletion of 3384bp.

Haploinsufficiency phenotype comments:

Mutations and deletion involving a single copy of the SALL1 gene cause Townes-Brocks syndrome (TBS), an autosomal dominant disorder. To date over 60 nonsense and frameshift mutations have been identified in SALL1. Biochemical and biological evidence indicate that truncated Sall1 transcripts produce stable protein and recapitulate the TBS phenotype, suggesting a dominant negative mechanism (PMIDs 12915476 and 12482848). In contrast, five heterozygous 'genomic' deletions have been described involving SALL1. These results suggest that SALL1 haploinsufficiency is sufficient to cause a TBS phenotype, although the previously reported correlation of a milder phenotype in individuals with deletions is a subject of ongoing debate.

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

Triplosensitivity phenotype comment:

No literature identified.