ClinGen Dosage Sensitivity Curation Page

DMXL2

  • Curation Status: Complete

Location Information

Select assembly: (NC_000015.9) (NC_000015.10)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Note: There are 2 reports of chimeric transcripts between CYP19 and DMXL2 which propose a gain of function for these mutations. PMID:17584767 Demura et al. (2007) examined 3 families and 2 sporadic cases with aromatase excess syndrome. CYP19 encodes aromatase, and gain of function mutations cause this syndrome. The authors describe a family with aromatase excess syndrome that have an abnormal chimeric CYP19 mRNA that is fused with exon 1 of DMXL2 (normally ~380 kb upstream of CYP19). They performed real-time PCR on 7 segments of DNA from exon 2 of DMXL2 to CYP19. In the affected mom and son, they found a ~145 kb deletion that includes exon 2 DMXL2 through the last exon of the gene. PMID:21470988 Fukami et al. (2011) identified chimeric transcripts in families with AES. They identified a ~212 kb deletion involving exons 2-43 of DMXL2 along with exons 5-10 of GLDN in one family. In three additional families, they identified a ~166 kb deletion involving exons 2-43 of DMXL2. These deletions resulted in a chimeric transcript including exon 1 of DMXL2 and CYP19A1 coding exons.

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