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

  • 0
    Haplo
    Score
  • 3
    Triplo
    Score

Region Facts

Region Name
22q11.21 recurrent (Cat eye syndrome) region (includes CECR2)
Cytoband
22q11.1-q11.21
Genomic Coordinates
GRCh37/hg19 chr22:17392953-18591860 NCBI Ensembl UCSC
GRCh38/hg38 chr22:16912063-18109094 NCBI Ensembl UCSC

Dosage Sensitivity Summary (Region)

Dosage ID:
ISCA-37393
Curation Status:
Complete
Issue Type:
Dosage Curation - Region
Description:
The 22q proximal region contains a cluster of low copy repeats (LCR) that mediate recurrent copy number changes through non-allelic homologous recombination. This review refers to CNVs between recurrent breakpoint LCR22-A and the LCRs on 22q11.1. Note that genes used as landmarks are not necessarily causative of the phenotype(s) associated with the region.
Haploinsufficiency:
No Evidence for Haploinsufficiency (0)
Triplosensitivity:
Sufficient Evidence for Triplosensitivity (3)
Related Links:
Last Evaluated:
02/27/2014

Haploinsufficiency (HI) Score Details

HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency (Disclaimer)
HI Evidence:
  • PUBMED: 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.
HI Evidence Comments:
Deletions of this region of 22q are rare in both the literature and in databases of genomic variation (both clinical and control populations).

Triplosensitivity (TS) Score Details

TS Score:
3
TS Evidence Strength:
Sufficient Evidence for Triplosensitivity (Disclaimer)
TS Disease:
TS Published Evidence:
  • PUBMED: 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.
  • PUBMED: 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.
  • PUBMED: 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.
TS Evidence Comments:
Cat eye syndrome (CES) results from tetrasomy/triplication (four copies) of the proximal region of chromosome 22q. Structurally, this gain presents in the form of a supernumerary marker chromosome (SMC) that is characterized cytogenetically as an inv dup(22)(pter-q11.2). Type I CES SMCs are symmetrical and contain two copies of the 22q11.1-q11.21 region, known as the CES critical region (CESCR). This region contains 22 genes, of which the genes CECR1 and CECR2 are considered to be candidates for heart/facial and neurologic/eye features, respectively. Type I SMCs result from rearrangements involving the most proximal low copy repeat (LCR-A) on chromosome 22 and do not involve the DiGeorge/Velocardiofacial syndrome region of 22q11.2. Phenotypic variability is in CES is common and may be attributed to variation in levels of mosaicism across different tissues.

Genomic View

Select assembly: (NC_000022.10) ()