ClinGen Dosage Sensitivity Curation Page

11p13 (WAGR syndrome) region

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for Triplosenstive Phenotype

Evidence for triplosensitivity phenotype
PubMed ID Description
23701296 Schilter et al. (2013) report a 6 year old girl with bilateral microphthalmia, congenital cataracts, glaucoma, abnormal pupil dilation, optic nerve hypoplasia, retinal detachment, borderline microcephaly, hypotonia, pituitary hypoplasia, and ADHD. She had an 877 kilobase duplication encompassing PAX6 and WT1 (hg19 coordinates: chr11:31609664-32486962). This duplication was inherited from her mother who had bilateral congenital cataracts, glaucoma, myopia, abnormal pupil dilation, corneal opacities, unilateral sensorineural hearing loss, and short stature. There was a strong maternal family history of similar clinical features but no other individuals were available for testing. Previous screening for mutations in SOX2, OTX2, PITX2, PITX3, FOXE3, and BMP4 was negative.

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.