ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
16086360 Kohlhase J et al. (2005) described 17 previously published and 5 novel pathogenic SALL4 variants associated with disease in patients with acro-renal-ocular syndrome or Duane radial-ray syndrome (i.e., Okihiro syndrome). All the described SALL4 variants were loss of function (8 nonsense and 14 frameshift).
30552424 Vanlerberghe C et al. (2019) sequenced SALL4 in patients originally diagnosed with Holt-Oram syndrome but lacking causative TBX5 variants. Eight patients were found to carry loss-of-function (8 frameshift and 2 nonsense) SALL4 variants and were thus re-diagnosed with Duane-radial ray syndrome (i.e., Okihiro syndrome).
17256792 Paradisi I and Arias S (2007) investigated a large multigenerational family with autosomal dominant IVIC syndrome. A frameshift variant in SALL4 was identified that segregated with disease among the 29 family members assessed (14 affected and 15 unaffected).

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.