ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000018.9) (NC_000018.10)
  • Haploinsufficiency score: 3
  • Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
17873119 Mutation and phenotype analysis was used in 80 unrelated patients of whom 65 met the clinical criteria for juvenile polyposis syndrome (typical JPS) and 15 were suspected to have JPS. Using MLPA, large genomic deletions involving the SMAD4 were found in six (9%) patients with typical JPS. Four exhibited a heterozygous deletion of all SMAD4 probes encompassing the entire SMAD4 gene and the promoter region. One patient had a deletion of coding exons 5-11 and another had a deletion of coding exons 6-11. All deletions were confirmed in a second independent MLPA test.
18178612 Archival material of 29 patients with JPS from 27 families was collected. MLPA identified a germline hemizygous large genomic deletion involving SMAD4 in a one patient.
18823382 DNA was extracted from 102 JPS probands. By MLPA, one proband had deletion of most of SMAD4 and another deletion of the 5' end of SMAD4.
  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

no identified literature.