ClinGen Dosage Sensitivity Curation Page

22q11.21 recurrent (Cat eye syndrome) region (includes CECR2)

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
16708226 Kriek et al. (2006) reported a proband with a deletion of the proximal 22q cat eye syndrome region and duplication of 22q11.2 DiGeorge syndrome region characterized by BAC array and MLPA. By FISH, the aberrations were found to be present on different copies of chromosome 22. Five normal relatives were found to carry the deleted copy of chromosome 22 suggesting that deletions affecting the cat eye syndrome may have no clinical relevance.

Evidence for Triplosenstive Phenotype

Evidence for triplosensitivity phenotype
PubMed ID Description
22890013 Belangero et al.(2012) reported four unrelated patients and three patients from the same family with supernumerary marker chromosomes 22 that were further characterized as type I rearrangements.
22495764 Kvarnung et al. (2012) reported four family members, a father and all his three children, with mosaicism for a supernumerary marker chromosome 22 that was further characterized as a CES type I rearrangement. Family members showed variable clinical findings, ranging from no obvious symptoms to classical cat eye syndrome. There was a direct correlation between the degree of mosaicism, as characterized by interphase FISH, and the degree of affectedness, particularly by examination of buccal mucosa.
11693792 Rosias et al. 2001 provided a review of 105 patients showing CES clinical features derived from tetrasomy of the CES critical region and compare to their patient with a SMC. Clinical phenotype varied widely, ranging from normal to severely affected with ear tags and pits being the most common feature.

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.