A 22;22 Robertsonian Translocation in a Patient with Repeated Abortions
Mohammad Ali Kiani BS*, Mohammad Reza Shakibaie PhD*, Mohammad Hassan Kariminejad MD**
*Department of Genetic Research Center, Kerman University of Medical Sciences, Kerman, Iran, **Kariminejad Pathology and Genetics Center, Tehran, Iran
Robertsonian translocation is one of the major chromosomal re-arrangements and comprises 18% of total genetic abnormalities. It occurs between different chromosomes and chromosomal segments and less than 0.2% of individuals carry a symptomatic chromosomal rearrangement. However, the t(22;22)is a rare phenomenon which mainly manifests as familial monosomy or trisomy. We report on a 30-year old woman who was referred to a pathological laboratory in Kerman, Iran. She had no mental retardation, but suffered from repeated abortions. On the basis of GTG-banding and karyotyping, it was found that a Robertsonian translocation in the chromosome 22;22 was the primary cause of this syndrome.
Keywords • Chromosome 22 • Robertsonian translocation • karyotype
Introduction
The human cell nucleus contains 23 pairs of chromosomes, on which lie 300,000 genes which carry the hereditary information.1 Reciprocal and non-reciprocal translocations are commonly observed among the chromosomes. This process involves the exchange of different chromosomal fragments.2 It is estimated that 0.2% of individuals carry a symptomatic chromosomal rearrangement.3 A special type of non-reciprocal translocation is Robertsonian translocation, in which the centromeric region of two acrocentric chromosomes fuse to form a single centromere. The resulting balanced karyotype has only 45 chromosomes including the translocated one, which in fact is made up of the long arms of two chromosomes.4 Robertsonian translocations are important in human genetics especially that it can be considered as a risk factor for Down’s syndrome.5 These types of chromosomal translocations are seen essentially in chromosomes group D including 13, 14, 15 and G including 21 and 22, in which the satellite chromosomes of the above groups encode genes for ribosomal RNA. Malsegregation of Robertsonian translocation results in trisomy or monosomy for complete chromosomes.6,10
Robertsonian translocations may be present in different family members but its penetrance in population is low. This report identifies a Robertsonian translocation in chromosome 22 in a woman with repeated abortions. As far as we know, this is the first instance reported in Iran.
Case Report
A 30-year-old woman and her 32-year-old husband were referred to a pathological laboratory in Kerman, Iran. They had no mental retardation or other genetic abnormalities. The woman gave a history of repeated abortions and karyotyping was therefore conducted as follows; 2 ml of peripheral blood from both subjects were collected in 5 ml heparinated (containing 0.1 ml of 1/10 diluted heparin [sigma grade]) tubes. Then 0.2 ml of the blood sample was added to 4 ml of HAM-F10 medium plus 1 ml of sterile fetal bovine serum, to which 0.2 ml of phytohemagglutinin was added. After 72 hours of incubation at 37° C, the cells were harvested at early metaphase by addition of 0.2 ml colcemid solution and prepared for GTG-banding (Gimsa Tripfin G-banding). Chromosomal banding was performed according to the method previously described.2
Figure 1 shows the karyotypes of a patient with non-mosaic and apparently balanced de novo Robertsonian translocation of chromosome 22. As the karyotype indicates, the centromeric region of two paired acrocentric chromosomes were completely fused to form a single centromere (shown with arrow). Fifteen metaphase spreads were studied by the GTG technique at 450-band resolution revealing 45 chromosomes with translocation of chromosome 22 and 22.
There were no phenotypic manifestations in carriers of such translocations, however, 100% of her gametes lead to offspring with abnormal karyotypes, either monosomy 22 or trisomy 22.
Discussion
A recent report by Shaikh et al9 indicates clustered 11q3 and 22q11 breakpoint and 3:1 miotic malsegregation in multiple unrelated t(11;22) families. Bolger et al3 reported a family in which the father and three children had meningiomas with clinical onsets at the ages of 35-65. The three siblings with meningiomas carried a constitutional Robertsonian translocation on chromosome 14 and 22. Rubes et al10 studied a possible effect on the development of bovine oocytes matured and fertilized in vitro, which was assessed on the basis of embryo yield and blastocyst formation. Oocytes fertilized with semen from two bulls, which were heterozygous for these translocations showed a significantly lower cleavage rate. Arab et al11 demonstrated a mosaic for a small marker chromosome resulting from a familial Robertsonian translocation (21;22). This marker is unusual because it is the result of a deletion of maternally inherited Robertsonian translocation. Similarly, Gualandi et al12 studied prenatal UPD testing survey in Robertsonian translocations. A systemic search was made for uniparental disomy (UPD) in familial Robertsonian translocations. The important finding was that no UPD cases were identified in the 23 cases analyzed. Morgan et al4 reported a woman with 42 autosomes due to engagement of both chromosome 14 in Robertsonian translocation. Choo et al5 described a new subfamily of human satellite III DNA which is represented on two different acrocentric chromosomes.
In our investigation, we found a unique Robertsonian translocation in chromosomes 22;22 which resulted in repeated abortions. As far as we know this is the first instance reported in Iran.
Acknowledgment
Our sincere thanks are due to Dr. Yazdanpanah for her cooperation during this investigation.
References