Balkan Journal of Medical Genetics

RING AUTOSOMES: SOME UNEXPECTED FINDINGS
Caba L1,*, Rusu C1,2, Plăiaşu V3, Gug G4,5, Grămescu M1, Bujoran C2, Ochiană D3, Voloşciuc M2, Popescu R1, Braha E1,2, Pânzaru M1,2, Butnariu L1,2, Sireteanu A1, Covic M1, Gorduza EV1
*Corresponding Author: Dr. Lavinia Caba, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Department of Medical Genetics, 16 Universitatii str., Iasi, 700115, Romania; Tel.: +40724962671; Email: lavinia_zanet@yahoo.com
page: 35

INTRODUCTION

Ring chromosomes are rare chromosomal abnormalities with an overall frequency of 1/30,000- 1/60,000 [1]. They are described for all human chromosomes and almost 50.0% of ring autosomes originated from acrocentric chromosomes [2]. In the majority of cases, the chromosomal abnormality is de novo and is formed during meiosis or early post zygotic divisions [3-5]. There are different formation mechanisms, the most frequent being breakage in both arms and fusion of the ends of the resulting centromeric fragment (these ends become sticky), with loss of terminal fragments. Another mechanism, demonstrated using high resolution molecular techniques, involves a telomere-to-telo-mere fusion that generates a pseudo-complete ring chromosome, associated with a small loss of genetic material responsible for cryptic deletions in the majority of cases [6-8]. The last mechanism described implies duplication with inversion associated with a terminal deletion [9,10]. Only 1.0% of all ring chromosomes are inherited, with demonstrated maternal origin in 90.0% of cases, while in men, the presence of a ring chromosome blocks spermatogenesis and induces infertility. Up to the present time, the reported inherited rings are derivatives of chromosomes 11, 14, 15, 17, 18, 20, 21 and 22 [11]. The ring chromosome can be detected in homogenous or mosaic form. In the first case, the anomaly originated in parental meiosis or in the early stages of embryogenesis. The mosaic abnormality can be explained by a mitotic non disjunction associated with ring instability. Some arguments for post zygotic origin of the anomaly was the detection of a line with monosomy in the case of small chromosomes (ring/ monosomy mosaicism) and the presence of a diploid normal line in the case of chromosomes rich in euchromatin (ring/normal line mosaicism) [3,4,12]. The presence of a ring chromosome induces a pheno-typic variability correlated with the size of lost genetic material and mitotic instability [9]. The severity of the phenotype depends on factors such as the length of the chromosome, the amount of euchromatin deleted, ring stability, presence of monosomic lines and other secondary aneuploid lines and the rate of mosaicism [13-17]. A familial variability was detected for inherited rings, but the phenotype is less severe than in sporadic rings [3,5,18]. A special condition called “ring syndrome” is characterized by severe growth retardation, but with a pseudo-normal phenotype (without major anomalies and with only a few minor dysmorphic features) [19]. In the largest study on ring chromosomes, Kosztolányi [5] showed that ring syndrome has a frequency of 20.0%. A plausible hypothesis for this syndrome’s relatively mild phenotype is the presence of an apparently complete ring chromosome without loss of genetic material, and thus, the phenotype does not depend on an implicated autosome. The mechanism proposed for growth retardation was ring instability that leads to cellular death [5,20]. A special mechanism was proposed for ring chromosomes that involve a large chromosome. In this case, a “dynamic mosaicism” was generated by sister chromatide exchanges that produce interlocked rings, broken rings, double rings or other anomalies [11,21].

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