Cytogenetic and molecular evaluation and 20‐year follow‐up of a patient with ring chromosome 14

Guilherme, Roberta Santos; Meloni, Vera de Freitas Ayres; Sodré, Claudete Palmer; Christofolini, Denise Maria; Pellegrino, Renata; Mello, Cláudia Berlim de; Conlin, Laura K.; Hutchinson, Anne L.; Spinner, Nancy B.; Brunoni, Décio; Kulikowski, Leslie Domenici; Melaragno, Maria Isabel

doi:10.1002/ajmg.a.33689

Cited by 11 publications

(7 citation statements)

References 19 publications

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“…Patient III with r(10) presents bilateral cryptorchidism and vesico-uretheral reflux although he has no deletion of RET, PAX2 , FGFR2, GFRA1 and EMX2 genes mapped in 10q, postulated as candidate genes for urinary and/or genital development [29]. Also, our patient with r(14) presented seizures and hypopigmented area in posterior pole in both eyes, which are features commonly found in individuals with a ring 14 and have been attributed to genes proximally located on 14q11q13 and q32.2, respectively [15,21,30]. Castermans et al [31] reported a patient with autism and coloboma, in which the ring formation was associated with silencing of the AMISYN gene, located near the breakpoint, also suggesting that the position effect can have clinical consequences possibly due to gene silencing.…”

Section: Discussionmentioning

confidence: 93%

Mechanisms of ring chromosome formation, ring instability and clinical consequences

et al. 2011

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BackgroundThe breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients.MethodsSeveral techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification) and FISH (Fluorescent in situ Hybridization).ResultsThe ring chromosomes of patients I to XIV were determined to be, respectively: r(3)(p26.1q29), r(4)(p16.3q35.2), r(10)(p15.3q26.2), r(10)(p15.3q26.13), r(13)(p13q31.1), r(13)(p13q34), r(14)(p13q32.33), r(15)(p13q26.2), r(18)(p11.32q22.2), r(18)(p11.32q21.33), r(18)(p11.21q23), r(22)(p13q13.33), r(22)(p13q13.2), and r(22)(p13q13.2). These rings were found to have been formed by different mechanisms, such as: breaks in both chromosome arms followed by end-to-end reunion (patients IV, VIII, IX, XI, XIII and XIV); a break in one chromosome arm followed by fusion with the subtelomeric region of the other (patients I and II); a break in one chromosome arm followed by fusion with the opposite telomeric region (patients III and X); fusion of two subtelomeric regions (patient VII); and telomere-telomere fusion (patient XII). Thus, the r(14) and one r(22) can be considered complete rings, since there was no loss of relevant genetic material. Two patients (V and VI) with r(13) showed duplication along with terminal deletion of 13q, one of them proved to be inverted, a mechanism known as inv-dup-del. Ring instability was detected by ring loss and secondary aberrations in all but three patients, who presented stable ring chromosomes (II, XIII and XIV).ConclusionsWe concluded that the clinical phenotype of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications and ring instability. Epigenetic factors due to the circular architecture of ring chromosomes must also be considered, since even complete ring chromosomes can result in phenotypic alterations, as observed in our patients with complete r(14) and r(22).

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Section: Discussionmentioning

confidence: 93%

Mechanisms of ring chromosome formation, ring instability and clinical consequences

et al. 2011

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“…Clones were selected from the BACPAC Resource Center at the Children's Hospital Oakland Research Institute (Oakland, CA, USA) and prepared according to Guilherme et al [12]. FISH was performed with whole chromosome painting (WCP) probes for chromosomes 6, 12 and 15 (Cytocell, Cambrigde, UK).…”

Section: Case Presentationmentioning

confidence: 99%

Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene

et al. 2012

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BackgroundThe majority of Marfan syndrome (MFS) cases is caused by mutations in the fibrillin-1 gene (FBN1), mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature.ResultsWe report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15.DiscussionThis is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.

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“…Patient 1 has a complete ring chromosome with no loss of genetic material, and yet she presents with phenotypic alterations and developmental abnormalities, which may be due to the configuration of the ring that could modify the genetic environment and gene expression due to epigenetic factors and to ring instability. Some complete ring chromosomes in patients with phenotypic abnormalities have been described in the literature before [Vermeesch et al, ; Le Caignec et al, ; Kosho et al, ; Guilherme et al, ].…”

Section: Discussionmentioning

confidence: 99%

Clinical, cytogenetic, and molecular characterization of six patients with ring chromosomes 22, including one with concomitant 22q11.2 deletion

Guilherme

Soares

Simioni

et al. 2014

American J of Med Genetics Pt A

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We report here on six patients with a ring chromosome 22 and the range of cytogenetic and phenotypic features presented by them. Genomic analysis was carried out using classical and molecular cytogenetics, MLPA (Multiplex Ligation-dependent Probe Amplification) and genome-wide SNP-array analysis. The ring was found in all patients, but Patient 6 displayed constitutional mosaicism with a normal cell line. Five patients had deletions in the ring chromosome 22, and in four of them the breakpoints--unique for each patient--could be identified by genome-wide SNP-array analysis. One patient presented with a 22q11.2 deletion concomitant with the deletion caused by the ring formation. Common phenotypic features included autism, speech delay and seizures, as previously reported for individuals with r(22) and/or 22q13.3 deletions. Investigation of the genes within the deletions revealed multiple genes related to development of the central nervous system, psychomotor delay, severe language impairment, hypotonia, and autistic symptoms. There was no clear correlation between the severity of clinical features and the size of the deleted segment. This study underscores the variability in ring structure and clinical presentation of the r(22) and adds information to the limited literature on this rare disorder.

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Cytogenetic and molecular evaluation and 20‐year follow‐up of a patient with ring chromosome 14

Cited by 11 publications

References 19 publications

Mechanisms of ring chromosome formation, ring instability and clinical consequences

Mechanisms of ring chromosome formation, ring instability and clinical consequences

Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene

Clinical, cytogenetic, and molecular characterization of six patients with ring chromosomes 22, including one with concomitant 22q11.2 deletion

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