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
17999358 Bondurand et al (2007) used a combination of semi-quantitative fluorescent multiplex polymerase chain reaction and FISH to search for SOX10 heterozygous deletions and describe the first characterization of SOX10 deletions in patients presenting with Waardenburg Syndrome Types 2 and 4. Both intragenic deletions and larger deletions involving SOX10 and surrounding genes were identified in individuals with both the WS4 and WS2 phenotypes, including individuals with neurologic involvement.
9462749 Pingault et al. (1998) describe two heterozygous, de novo nonsense mutations (E189X and Y83X) in two unrelated individuals with clinical diagnoses of WS4.
10077527 Southard-Smith et al. (1999) describes mutations identified in SOX10, including a heterozygous, de novo nonsense mutation (Y207X) in an individual with a clinical diagnosis of WS4.

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.