Twenty-year cytogenetic and molecular follow-up of a patient with ring chromosome 15: a case report

Abstract

IntroductionRing chromosome 15 is a rare disorder, with only a few over 40 cases reported in the literature. There are only two previous reports of cases where patients with ring chromosome 15 have been followed-up.Case presentationWe report here on the 20-year clinical and cytogenetic follow-up of a patient with a ring chromosome 15. Our patient, a Caucasoid Asian woman, presented with short stature, microcephaly, minor dysmorphic features, hyperextensible knees, generalized hirsutism, café-au-lait and small hypochromic spots spread over her face and the front of her chest and abdomen, dorsolumbar scoliosis and mild intellectual disability. She was followed-up from the age of eight to 28 years. When she was 27 years old, she was reported by her mother to present with compulsive overeating and an aggressive mood when challenged. Karyotyping revealed that the majority of her cells harbored one normal chromosome and one ring chromosome. Silver staining revealed the presence of the nucleolar organizer region in the ring chromosome. Ring loss and/or secondary aberrations exhibited a slight increase over time, from 4.67% in 1989 to 7.67% in 2009, with the presence of two monocentric rings, cells with interlocked rings, a dicentric ring, and broken or open rings. A genome-wide array technique detected a 5.5Mb deletion in 15q26.2.ConclusionsWe observed that some phenotypic alterations in our patient can be associated with gene loss and haploinsufficiency. Other features may be related to different factors, including ring instability and epigenetic factors.

Array Characterization of Prenatally Diagnosed 15q26 Microdeletion and 2q37.1 Duplication: Report of a New Case with Multicystic Kidneys and Review of the Literature

“…an associated deletion or overexpression of some modifier genes, could explain the absence of renal defects in some cases of COUPTF2 haploinsufficiency. 9,19 Exploration of this gene lesion should probably be considered in kidney pathology investigations.…”

“…Further characterization of similar cases is of great importance for a more precise genotype-phenotype correlation and for a better understanding of the role of this gene in human kidney development. 27 (C), 33 (D), 19 (E), 16 (F), 8 (G), 35 (H), 25 (I), 26 and (J). 20…”

Small supernumerary marker chromosome 15 and a ring chromosome 15 associated with a 15q26.3 deletion excluding the IGF1R gene

“…Ring chromosomes are formed by two breaks occurring on the same chromosome followed by joining of the broken ends and result in a ring. The structural and behavioral instability of ring chromosomes is described (Guilherme et al, ; Kistenmacher & Punnett, ; McClintock, ), which could be associated to a single (or an uneven number) or two (or an even number) sister chromatid exchanges during the ring replication. Their instability could lead to the variation in the size and the number of the rings, variation in the number of centromeres, the occurrence of interlocked rings, and the presence of different chromosome fragments.…”

“…Ring chromosome 15 [r(15)] has been described in connection with dysmorphic features and may cause several phenotypes including cognitive disability, growth deficiency, triangular facies, and brachydactyly (Butler et al, ; Guilherme et al, ; Roback et al, ). Growth deficiency, developmental delay, eye abnormalities (macular defects, hyperopia, strabismus, and heterochromia), dysplastic ears and hearing defects, café‐au‐lait spots and cardiac anomalies are the most common features of patients with ring (15) syndrome.…”

Molecular characterization and evaluation of complex rearrangements in a case of ring chromosome 15

“…Ring chromosome 15 is associated with a rare disorder that was first described by Jacobsen in 1966 [ 1 ]. Around 50 cases with r(15) have been reported till date, with only a few cases being comprehensively characterized using molecular cytogenetic techniques [ 2 , 3 ]. Major clinical features include severe pre- and postnatal growth delay, microcephaly, triangular face, hypertelorism, intellectual disability, clinodactyly and brachydactyly of the fifth finger, small hands and feet, and cafe-au-lait spots [ 2 , 4 , 5 ].…”