ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000017.10) (NC_000017.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
10720943 Bingham et al. (2000) sequenced HNF1B in 6 patients with maturity-onset diabetes of the young (MODY) and found a de novo 5 bp deletion in exon 4 in one proband. The proband was also found to have small renal cysts and impaired renal function. The HNF1B variant was present in the proband's son who had multicystic, dysplastic kidneys.
15068978 Bellann?-Chantelot et al. (2004) report 8 new variants in HNF1B in patients with MODY5. Two nonsense variants (one was de novo) and one de novo splice site mutation were identified. All probands were found to have renal involvement including structural abnormalities and impaired kidney function. Mutations were not detected in 212 normal control chromosomes.
9398836 Horikawa et al. (1997) sequenced HNF1B in 57 probands with MODY. They found a nonsense variant (R177X) in a proband and the affected sister and mother. The variant was not found in 53 unrelated normal controls.

Haploinsufficiency phenotype comments:

Loss of function variants in HNF1 have been associated with renal cysts and diabetes syndrome. Additional cases: PMID 15930087 Edghill et al. (2006) identified 13 new probands with HNF1B variants from a cohort 160 patients with unexplained renal disease, with or without diabetes. Seven variants were predicted to be loss of function, including 3 nonsense, 2 frameshift and 2 splice site variants. Familial studies were performed for 6 of the probands with loss of function variants. HNF1B variants were detected in 10 affected family members across the 6 families with at least one segregation per family. Variants were absent in 6 unaffected family members.

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

Triplosensitivity phenotype comment:

Located within the 17q12 duplication syndrome (614526). Note: Mefford et al. (2007) PMID:17924346 idenfied a complex duplication in a patient with intellectual disability and seizures. A 27 kb duplication involves LHX1 and a second 259 kb duplication includes HNF1B. Both duplications are present in the unaffected mother.