ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

  • 12q24.21
  • GRCh37/hg19 chr12: 115,108,059-115,121,969
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr12: 114,670,254-114,684,164
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000012.11) (NC_000012.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
12116211 Sasaki et al. (2002): Describes two affected brothers and an affected mother with a K273X nonsense mutation not seen in 20 normal controls.
10330342 Bamshad et al. 1999: Describes mutations found in 10 unrelated families, including the Q360X and S343X nonsense mutations.

Haploinsufficiency phenotype comments:

Mutations in TBX3 have been associated with ulnar-mammary syndrome. Variable expressivity has been well-documented for this syndrome. Genomic deletions involving TBX3 have been described in individuals with features of ulnar-mammary syndrome. Of note, Klopocki et al. (2006) describe a child with features of UMS as well as dysmorphic features and intellectual disability (not typical features of UMS) (PMID:16896345). Using a whole-genome tiling path BAC array, an interstitial deletion on chromosome 12q24.21 was detected. The two breakpoints were located between RP11-636B16 and RP11-297J16 (proximal breakpoint) and RP11-8A1 and RP11-115H15 (distal breakpoint). The size of the deletion was determined to be ranging from 113.6 to 114.9 Mb. TBX3 was noted to be the only known gene located within the deleted region (positions 113.57-113.58 Mb). The authors note that, though TBX3 was thought to be the only known gene in the region, they could not rule out the possibility that positional effects or other non-coding sequences of the deleted interval regulating the expression of nearby genes played a role in her severe phenotype. Borozdin et al. (2006) describe a mother and daughter with features of both ulnar-mammary and Holt-Oram syndrome with a contiguous deletion involving TBX3 and TBX5 (PMID: 16892408).

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