A de novo sSMC(22) Characterized by High-Resolution Arrays in a Girl with Cat-Eye Syndrome without Coloboma

Abstract

Cat-eye syndrome (CES) results from trisomy or tetrasomy of proximal 22q originated by a small supernumerary marker chromosome (sSMC). Two critical regions for the major clinical features of CES (CESCRs) have been suggested; however, CES clinical presentation often does not correlate with the sSMC genetic content. We report here a CES girl without coloboma and carrier of a de novo type I sSMC(22) as determined by G- and C-banding, NOR staining and microarrays. This sSMC included 6 distal genes outside the original CESCR and led to a tetrasomy for 22q11.1–22q11.21. The patient’s final karyotype was 47,XX,+psu dic(22)(q11.21).arr 22q11.1q11.21(15,250,000–17,035,860)×4 dn. The amplified region outside of CESCR included some genes that may be related to neurologic, heart and renal abnormalities. Conversely, even though the amplification included the CECR2 gene, a major candidate for eye features, there was no coloboma in the patient. The genetic delineation of the present sSMC further strengthens that the CES clinical presentation does not fit completely with the duplicated genetic content and that CES is actually a genomic disorder. Furthermore, since we observed no mosaicism, we believe that other mechanisms might be behind the variability of CES phenotypes as well, mainly those related with functional interactions among amplified genes.

A de novo atypical ring sSMC(22) characterized by array CGH in a boy with cat-eye syndrome

“…All of the proximal and distal duplication breakpoints of the ring sSMC stretched into the largest, LCR22-A region which is considered to be the recurrent proximal deletion endpoint of TDR seen in 85% of 22q11.2 deletion syndrome cases (Figure 5a, b) [1]. However, similar breakpoints and even the same gene content have been published [12,13], were not specifically in ring shape. The reported ring 22 chromosomes were accompanied by the absence of normal chromosome and/or were the results of centric fission 22 [11,14-16].…”

“…A similar but smaller double ring sSMC(22) was described by Mears et al in 1995 [ 4 ]. The fact that both patients (published by Mears and presented here) were carriers of a smaller than typical type I CES with four copies of CECR1 and possessed all main CES abnormalities suggests that CECR1 gene dosage and functional interactions among amplified genes [ 12 ] are the predictable determining factor to express the CES phenotype and the size of sSMC(22) is rather a contributing factor to phenotypic variability.…”

Cat-Eye Syndrome: A Report of Two Cases and Literature Review

“…Cat-eye syndrome stems from trisomy or tetrasomy of the proximal long (q) arm of chromosome 22, which derives from sSMC [1][2][3]. The diagnosis of sSMC may require molecular and cytogenetic studies, including chromosomal analysis by karyotyping, fluorescent in situ hybridization (FISH), and array CGH [3,[4][5][6][7].…”

“…Prenatal diagnosis is always a challenge since the fetal ultrasound findings are unspecific, but an sSMC of chromosome 22 detected at amniocentesis should alert CES [7][8][9]. In both cases, CES was never suspected before birth, and amniocentesis was not performed.…”

Prenatal diagnosis and molecular cytogenetic identification of small supernumerary marker chromosomes: analysis of three prenatal cases using chromosome microarray analysis

“…However, prenatal ultrasound did not detect eye or kidney anomalies. Multiple cases have been reported involving candidate CECR2 gene without ocular defects [ 23 , 24 ]. Therefore, except for the gene dose effect, the interaction of upstream and downstream regulating elements of the above-mentioned genes, as well as gene-environment interactions, may be responsible for the penetrance and phenotype differences associated with CES.…”