Clinical, Cytogenetic and Molecular Study in a Case of r(3) with 3p Deletion and Review of the Literature

Abstract

Ring chromosome 3 is a rare abnormality with only 10 patients described in the literature. We report a patient with r(3) and ∼6-Mb distal 3p deletion. Single nucleotide polymorphism array, multiplex ligation-dependent probe amplification and fluorescence in situ hybridization techniques revealed that the ring was formed by a break in 3p26.1 and fusion with the subtelomeric region of 3q. The patient presents delayed psychomotor development, growth failure, minor anomalies and other features similar to patients with 3p monosomy. The analysis of 300 metaphase cells using G-banding and fluorescence in situ hybridization with centromeric probe revealed ring instability resulting in cells with secondary aberrations and with ring loss that could also be related to some phenotypic characteristics such as growth delay. This is the first patient with r(3) studied using molecular techniques that determined the exact breakpoints in order to establish a better karyotype-phenotype correlation.

Chromosome r(3)(p25.3q29) in a Patient with Developmental Delay and Congenital Heart Defects: A Case Report and a Brief Literature Review

“…Our patient shared some of the phenotypes found in other patients with r(3) and 3p deletion syndrome, such as growth failure, developmental delay, mental retardation, microcephaly, dysmorphism, and ptosis as well as an additional CHD which has not been observed in r(3) patients but has been reported in about 30% of patients with 3p deletion syndrome [Shuib et al, 2009;Guilherme et al, 2011a]. The 3p deletion syndrome is a contiguous gene syndrome caused by deletions of variable lengths of the 3pterp25 region that is rather well defined since it was first reported in 1978 and has some common features with r(3), despite the low number of reported cases [Kitatani et al, 1984;Teyssier et al, 1991;Malmgren et al, 2007;Pohjola et al, 2010;Guilherme et al, 2011a;Kaur and Khetarpal, 2013].…”

“…It is reported that most patients with a ring chromosome displayed ring instability [Guilherme et al, 2013]. A ring chromosome is considered unstable when it produces secondary aberrations in more than 5% of cells [Kosztolányi et al, 1987;Guilherme et al, 2011a]. The unstable r(3) was observed in our patient with ring instability in 9.67% of the cells.…”

“…Guilherme et al [2011a] identified a 5.7-Mb deletion with the exact breakpoints at 3p (chr3: 307,820-6,045,520) involving 16 genes in a 16-year-old boy with r(3) using a whole-genome microarray (Affymetrix SNP 6.0 array) for the first time. Earlier cases with r(3) were determined only by conventional cytogenetic techniques including chromosome karyotyping and/or FISH without exact information on breakpoints and involved genes.…”

“…The phenotypic inconsistency of the cases was considered to be associated with differences of the deletion sizes and affected genes [Kosztolányi, 1987;Guilherme et al, 2011a, b]. Previous studies have suggested that the genes responsible for the main clinical features were most likely located within a minimal region of overlap named MRO [Malmgren et al, 2007;Guilherme et al, 2011a] and this region contained 12 genes such as CNTN4, IL5RA, TRNT1, CRBN, LRRN1, SETMAR, SUMF1, ITPR1, EGOT, BHLHE40, ARL8B, EDEM1 . Peltekova et al [2012] suggested that a 518-kb region containing 12 genes (including THUMPD3 , SETD5, LHFPL4, MTMR14, CPNE9, BRPF1, OGG1, CAMK1, TADA3, ARPC4, TTLL3, and RPUSD3 ) might be a critical region by studying a patient with a typical 3p deletion syndrome.…”

Bilateral anterior segment dysgenesis in an infant with partial trisomy 16q and partial monosomy 3p

“…4,5 This chromosomal abnormality is associated with prenatal and postnatal growth deficiency, cognitive impairment, distinctive craniofacial malformations, synophrys, and hypertrichosis. 6 The following ophthalmic associations have been reported: ptosis, iris coloboma, upward-slanting eyelids, and wide-set eyes.…”