35-Year Follow-Up of a Case of Ring Chromosome 2: Array-CGH Analysis and Literature Review of the Ring Syndrome

Côté et al. [1981] suggested that ring chromosomes with or without deletions share a common pattern of phenotypic anomalies, regardless of which chromosome is involved. The phenotype of this ‘general ring syndrome' consists of growth failure without malformations, few or no minor anomalies, and mild to moderate mental retardation. We reconsidered the ring chromosome 2 case previously published by Côté et al. [1981], and we characterized it by array CGH, polymorphic markers as well as subtelomere MLPA and FISH analysis. A terminal deletion (q37.3qter) of maternal origin of the long arm of the ring chromosome 2 was detected and confirmed by all the above-mentioned methods. Ring chromosome 2 cases are exceedingly rare. Only 18 cases, including the present one, have been published so far, and our patient is the longest reported survivor, with a 35-year follow-up, and the third case characterized by array-CGH analysis.

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Ring chromosome 2 in a child with growth failure and few congenital abnormalities

American Journal of Medical Genetics ◽

10.1002/ajmg.1320070321 ◽

1980 ◽

Vol 7 (3) ◽

pp. 383-389 ◽

Cited By ~ 10

Author(s):

Norman V. Vigfusson ◽

Kennard J. Kapstafer ◽

Marilyn A. Lloyd ◽

John M. Optiz

Keyword(s):

Congenital Abnormalities ◽

Growth Failure ◽

Ring Chromosome ◽

Chromosome 2

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Prenatal diagnosis of ring chromosome 13: a rare chromosomal aberration

Case Reports in Perinatal Medicine ◽

10.1515/crpm-2017-0050 ◽

2018 ◽

Vol 7 (2) ◽

Author(s):

Haruka Goto ◽

Yasuyuki Fujita ◽

Yuka Sato ◽

Saki Kido ◽

Masanobu Ogawa ◽

...

Keyword(s):

Chromosomal Aberration ◽

Good Condition ◽

Ring Chromosome ◽

Japanese Woman ◽

Trisomy 13 ◽

Fish Analysis ◽

Chromosome 13 ◽

Ring Chromosomes ◽

Banding Analysis ◽

Female Baby

Abstract We report the case of a 24-year-old Japanese woman, gravida 2, para 1, who became pregnant spontaneously. At 24 weeks of gestation, her fetus was found to have various abnormalities, including holoprosencephaly, congenital heart disease and severe fetal growth restriction, and she was referred to our hospital. From these findings, the fetus was suspected of having a chromosomal aberration, in particular, trisomy 13, and after genetic counseling, amniocentesis for chromosomal analysis was performed. Although the results of fluorescent in situ hybridization (FISH) analysis showed no numeric abnormalities, G-banding analysis revealed a ring chromosome 13; 46, XX, r (13) (p13q32). At 41 weeks of gestation, she delivered a female baby weighing 2240 g with good condition. The respiratory status of the neonate was stable, and she was discharged 30 days after birth. Ring chromosomes are rare chromosomal aberrations, and obstetricians should recognize that ring chromosomes cannot be detected solely by FISH analysis and require G-banding analysis and that information on the ring breakpoint is needed to counsel the parents regarding the fetal and neonatal prognosis.

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Clinico-radiological and molecular characterization of a child with ring chromosome 2 presenting growth failure, microcephaly, kidney and brain malformations

Molecular Cytogenetics ◽

10.1186/s13039-015-0121-z ◽

2015 ◽

Vol 8 (1) ◽

pp. 17 ◽

Cited By ~ 3

Author(s):

Mariasavina Severino ◽

Andrea Accogli ◽

Giorgio Gimelli ◽

Andrea Rossi ◽

Svetlana Kotzeva ◽

...

Keyword(s):

Molecular Characterization ◽

Growth Failure ◽

Ring Chromosome ◽

Chromosome 2 ◽

Brain Malformations

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Prenatal Diagnosis of 4p and 4q Subtelomeric Microdeletion in De Novo Ring Chromosome 4

Case Reports in Obstetrics and Gynecology ◽

10.1155/2013/248050 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5

Author(s):

Halit Akbas ◽

Naci Cine ◽

Mahmut Erdemoglu ◽

Ahmet Engin Atay ◽

Selda Simsek ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Critical Region ◽

Array Cgh ◽

De Novo ◽

Ring Chromosome ◽

Maternal Serum ◽

Chromosome 4 ◽

Maternal Serum Screening ◽

Ring Chromosomes ◽

Subtelomeric Deletion

Ring chromosomes are unusual abnormalities that are observed in prenatal diagnosis. A 23-year-old patient (gravida 1, para 0) referred for amniocentesis due to abnormal maternal serum screening result in the 16th week of second pregnancy. Cytogenetic analysis of cultured amniyotic fluid cells revealed out ring chromosome 4. Both maternal and paternal karyotypes were normal. Terminal deletion was observed in both 4p and 4q arms of ring chromosome 4 by fluorescence in situ hybridization (FISH). However deletion was not observed in the WHS critical region of both normal and ring chromosome 4 by an additional FISH study. These results were confirmed by means of array-CGH showing terminal deletions on 4p16.3 (130 kb) and 4q35.2 (2.449 Mb). In the 21th week of pregnancy, no gross anomalia, except two weeks symmetric growth retardation, was present in the fetal ultrasonographic examination. According to our review of literature, this is the first prenatal case with 4p and 4q subtelomeric deletion of ring chromosome 4 without the involvement of WHS critical region. Our report describes the prenatal case with a ring chromosome 4 abnormality completely characterized by array-CGH which provided complementary data for genetic counseling of prenatal diagnosis.

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Ring chromosome 3 instability at mitosis

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2019.09.40-45 ◽

2019 ◽

pp. 40-45

Author(s):

Н.В. Шилова ◽

М.Е. Миньженкова ◽

Ж.Г. Маркова ◽

А.А. Тарлычева ◽

Д.А. Юрченко

Keyword(s):

Ring Chromosome ◽

Postnatal Growth ◽

Chromosome 3 ◽

Fish Analysis ◽

Developmental Abnormalities ◽

Dysmorphic Features ◽

Severe Intellectual Disability ◽

Ring Chromosomes ◽

Mitotic Instability ◽

Variable Phenotype

Актуальность. Кольцевая хромосома 3 - редкая хромосомная аномалия, характеризующаяся выраженной вариабельностью фенотипических отклонений. Наиболее характерными проявлениями присутствия в кариотипе кольцевой хромосомы 3 являются пре- и постнатальная задержка роста, задержка психомоторного развития, микроцефалия и другие аномалии развития. Кольцевая структура может приводить к нарушению нормального расхождения хромосом при клеточном делении и вызывает митотическую нестабильность, приводящую к динамическому мозаицизму. В данном сообщении представлен случай митотической нестабильности кольцевой хромосомы 3 у ребенка с множественными пороками и аномалиями развития, демонстрирующий влияние вторичного хромосомного дисбаланса на степень выраженности фенотипических аномалий. Цель: исследование митотической нестабильности кольцевой хромосомы 3. Методы: FISH с ДНК-зондами на хромосому 3. Результаты. При стандартном цитогенетическом исследовании определен кариотип 46,XX,r(3)(p26q29). При FISH-анализе обнаружено наличие нескольких клонов клеток, содержащих различные варианты аномальных по структуре производных кольцевой хромосомы 3. Выводы. Присутствие кольцевых хромосом в геноме является причиной митотической нестабильности, что приводит к формированию соматического динамического мозаицизма. Соматический динамический мозаицизм, вследствие которого образуются клоны клеток с различным хромосомным дисбалансом, вносит существенный вклад в формирование аномального фенотипа. Ring chromosome 3 is a rare chromosomal abnormality with a highly variable phenotype principally characterized by pre- and postnatal growth retardation, developmental delay, mild to severe intellectual disability, microcephaly and mild dysmorphic features. The presence of a ring chromosome causes mitotic instability and often results in dynamic mosaicism with cells showing chromosomal or segmental aneuploidies and leading to various phenotypic consequences. We present a case of mitotic instability of ring chromosome 3 in a child with multiple malformations and developmental abnormalities. Aim: The investigation of ring chromosome 3 instability at mitosis. Methods: FISH with DNA probe on chromosome 3. Results: The karyotype of a child - 46,XX,r(3)(p26q29). FISH analysis revealed a mosaic clones derived from ring chromosome 3. Conclusions: The ring chromosomes are unstable at mitosis and lead to the formation of somatic dynamic mosaicism. Mitotic instability of ring chromosome 3 demonstrates the influence of secondary genetic imbalance on severity of symptoms in our patient.

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An Interstitial 4q Deletion with a Mosaic Complementary Ring Chromosome in a Child with Dysmorphism, Linear Skin Pigmentation, and Hepatomegaly

Case Reports in Genetics ◽

10.1155/2017/4894515 ◽

2017 ◽

Vol 2017 ◽

pp. 1-4

Author(s):

J. Carter ◽

H. Brittain ◽

D. Morrogh ◽

N. Lench ◽

J. J. Waters

Keyword(s):

Array Cgh ◽

Skin Pigmentation ◽

Ring Chromosome ◽

Microarray Platform ◽

Integrated Approach ◽

Small Ring ◽

Fish Analysis ◽

Copy Number Loss ◽

Genome Wide ◽

Microarray Studies

Interstitial deletions of 4q are rarely reported, vary in size, and have limited genotype-phenotype correlations. Here, genome-wide array CGH analysis identified a 21.6 Mb region of copy number loss at 4q12-q21.1 in a patient diagnosed with dysmorphism, linear skin pigmentation, and hepatomegaly. An additional small ring chromosome was detected in 5/30 cells examined via G-banding. Confirmation of the origin of the ring chromosome was obtained by FISH analysis which identified that the ring chromosome contained material from the deleted region of chromosome 4 and was therefore complementary to the 21.6 Mb deletion. Further microarray studies in the proband using a different microarray platform showed no evidence of mosaicism. This case highlights the importance of an integrated approach to cytogenetic analysis and demonstrates the value of G-banding for detecting mosaicism, as current microarray platforms are unable to detect low level mosaics.

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46,XY,r(8)/45,XY,−8 Mosaicism as a Possible Mechanism of the Imprinted Birk-Barel Syndrome: A Case Study

Genes ◽

10.3390/genes11121473 ◽

2020 ◽

Vol 11 (12) ◽

pp. 1473

Author(s):

Anna A. Kashevarova ◽

Tatyana V. Nikitina ◽

Larisa I. Mikhailik ◽

Elena O. Belyaeva ◽

Stanislav A. Vasilyev ◽

...

Keyword(s):

De Novo ◽

Snp Array ◽

Ring Chromosome ◽

Chromosome 8 ◽

Fish Analysis ◽

Feeding Problems ◽

Maternal Chromosome ◽

Imprinting Disorder ◽

Ring Chromosomes ◽

Normal Copy Number

Ring chromosome 8 (r(8)) is one of the least frequent ring chromosomes. Usually, maternal chromosome 8 forms a ring, which can be lost from cells due to mitotic instability. The 8q24 region contains the imprinted KCNK9 gene, which is expressed from the maternal allele. Heterozygous KCNK9 mutations are associated with the imprinting disorder Birk-Barel syndrome. Here, we report a 2.5-year-old boy with developmental delay, microcephaly, dysmorphic features, diffuse muscle hypotonia, feeding problems, motor alalia and noncoarse neurogenic type of disturbance of muscle electrogenesis, partially overlapping with Birk-Barel syndrome phenotype. Cytogenetic analysis of lymphocytes revealed his karyotype to be 46,XY,r(8)(p23q24.3)[27]/45,XY,−8[3]. A de novo 7.9 Mb terminal 8p23.3p23.1 deletion, a 27.1 Mb 8p23.1p11.22 duplication, and a 4.4 Mb intact segment with a normal copy number located between them, as well as a 154-kb maternal LINGO2 gene deletion (9p21.2) with unknown clinical significance were identified by aCGH + SNP array. These aberrations were confirmed by real-time PCR. According to FISH analysis, the 8p23.1-p11.22 duplication was inverted. The ring chromosome originated from maternal chromosome 8. Targeted massive parallel sequencing did not reveal the KCNK9 mutations associated with Birk-Barel syndrome. Our data allow to assume that autosomal monosomy with inactive allele of imprinted gene arising from the loss of a ring chromosome in some somatic cells may be an etiological mechanism of mosaic imprinting disorders, presumably with less severe phenotype.

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Bilateral Phyllodes Giant Tumor. A Case Report Analyzed by Array-CGH

Diagnostics ◽

10.3390/diagnostics10100825 ◽

2020 ◽

Vol 10 (10) ◽

pp. 825

Author(s):

Francesco Fortarezza ◽

Federica Pezzuto ◽

Gerardo Cazzato ◽

Clelia Punzo ◽

Antonio d’Amati ◽

...

Keyword(s):

Array Cgh ◽

Phyllodes Tumor ◽

Molecular Classification ◽

Left Breast ◽

Comparative Genomic ◽

Fish Analysis ◽

Molecular Tests ◽

Giant Tumor ◽

Metastatic Risk ◽

The Right

The breast phyllodes tumor is a biphasic tumor that accounts for less than of 1% of all breast neoplasms. It is classified as benign, borderline, or malignant, and can mimic benign masses. Some recurrent alterations have been identified. However, a precise molecular classification of these tumors has not yet been established. Herein, we describe a case of a 43-year-old woman that was admitted to the emergency room for a significant bleeding from the breast skin. A voluminous ulcerative mass of the left breast and multiple nodules with micro-calcifications on the right side were detected at a physical examination. A left total mastectomy and a nodulectomy of the right breast was performed. The histological diagnosis of the surgical specimens reported a bilateral giant phyllodes tumor, showing malignant features on the left and borderline characteristics associated with a fibroadenoma on the right. A further molecular analysis was carried out by an array-Comparative Genomic Hybridization (CGH) to characterize copy-number alterations. Many losses were detected in the malignant mass, involving several tumor suppressor genes. These findings could explain the malignant growth and the metastatic risk. In our study, genomic profiling by an array-CGH revealed a greater chromosomal instability in the borderline mass (40 total defects) than in the malignant (19 total defects) giant phyllodes tumor, reflecting the tumor heterogeneity. Should our results be confirmed with more sensitive and specific molecular tests (DNA sequencing and FISH analysis), they could allow a better selection of patients with adverse pathological features, thus optimizing and improving patient’s management.

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