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Short Article Isolated cell translocations: are they significant?

R. R. Devi, R. Sayee
Division Of Human Genetics (DHG), Department of Anatomy, St. Johns Medical College, Bangalore, India

BACKGROUND: Cytogenetics study using cultured Tlymphocytes derived from peripheral blood is the easiest way to study human chromosome complement and it is also an excellent method to study chromosomal abnormalities: either structural or numerical. The structural chromosomal abnormalities include translocations, deletions, duplications, ring chromosomes and isochromosomes. AIMS : Cases presenting with multiple congenital anomalies, mental retardation, pregnancy wastage or abnormalities in sexual function are referred to the Division of Human Genetics to rule out chromosomal anomalies. METHODS AND MATERIALS: A total of 70 cases with multiple congenital anomalies, mental retardation, pregnancy wastage or abnormalities in sexual function were studied. About 72 h cultured peripheral lymphocytes subjected to GTG banding were analyzed to look at the chromosome profile. RESULTS: Out of 70 cases of reciprocal translocation, single cell translocations were seen in ten cases (three females; seven males). Looking at the case profile, it was seen that they were referred for mental retardation, bad obstetric history and hypogonadism. It was seen that seven cases (70%) had t(7;14), two (20%) had complex translocations: t(X;9;8) and t(2;10;11), and one (10%) had t(4;21). CONCLUSIONS : Depending on the phenotype, the patients were informed of their abnormality and the need for a look out for the development of any associated problems. Key words: Chromosomal abnormality; GTG banding; Tlymphocyte; translocation.

chromosomal abnormalities, either structural or numerical. For all practical purposes, the peripheral lymphocytes are one of the most easily accessible tissue representatives of the human body. Spontaneous constitutional chromosomal abnormalities, when it disrupts a DNA sequence or an important gene, may present as various phenotypic manifestations viz. dysmorphic features, mental retardation, metabolic disorders, abnormalities of sexual function and the like. The structural chromosomal abnormalities include translocations, deletions, duplications, ring chromosomes and isochromosomes. Some of these chromosomal aberrations have been considered to be of not much importance and are classified as polymorphic variants. [1],[2] This article is aimed at discussing isolated cell translocations seen on routine chromosome analyses. Methods and materials

In the various cases presenting with multiple congenital anomalies, mental retardation, pregnancy wastage or abnormalities in sexual function referred to the Division of Human Genetics to rule out chromosomal anomalies, 72 h cultured peripheral lymphocytes subjected to GTG banding[3] was analyzed to look at the chromosome profile. On an average, 20 metaphase spreads are routinely analyzed and in the event of noticing an abnormality, 30 more spreads are analyzed.

Cytogenetics studies using cultured T-lymphocytes derived from peripheral blood are considered to be the easiest way to study human chromosome complement and they are also excellent methods to study

Address for Correspondence : RR Devi, Division Of Human Genetics, Department of Anatomy, St. Johns Medical College, Bangalore 560 034, India E-mail: sjmcdhg@yahoo.co.in Indian Journal of Human Genetics May-August 2005 Volume 11 Issue 2

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Devi and Sayee

Results

Single cell reciprocal translocations were seen in ten cases (three females; seven males). It was seen that they were referred for mental retardation (four cases, all males), bad obstetric history (BOH) (five cases three females, two males) and one male for hypogonadism. Of these, seven cases (70%) had t(7;14); two patients (20%) had complex translocations t(X;9;8) and t(2;10;11) and one (10%) had t(4;21) [Table 1]. Discussion

cell translocations were seen in cases presenting with BOH. Previous studies have also reported a higher incidence of translocation anomalies in cases presenting with spontaneous abortions. Probably these types of structural anomalies may lead to a greater instability of the chromosomes that ultimately manifests as spontaneous abortions and/or giving birth to children with multiple congenital anomalies in the case of habitual aborters. The location of the breakpoints, the size of the translocated segment of the chromosome probably has a role in determining the phenotypic expression.[4] The origin and effect of these isolated translocations has led to many assumptions. In the case of the isolated translocations seen in the females, probably they represent the fetal trophoblasts that might have escaped into the maternal circulation from the previous pregnancy.[4] The common breakpoints noticed in t(7;14) are at 7p1315, 7q35, and 14q11.[1],[46] Two constant g chain genes involved in site specific somatic rearrangements during T cell differentiation are located in 7p15 region and hence these translocations may affect the development of the immune response. Probably, these translocations may be an indication of the malignant transformation of the T cells in future [7] The presence of these t(7;14) in individuals not known to have any malignancy or predisposition to increased chromosome breakage suggest that this may be normally seen in routine cytogenetics procedures and it might be due to the influence of one of the following factors: Viral aetiological agents like Mycoplasma/ alteration in DNA repair mechanism/extraneous factors like PHA involved in the in-vitro culture.[8] Possibly, some selective advantage is conferred by the translocation or the spatial arrangement of the chromosome in the cell.[5] Be it an in-vivo or in an in-vitro after effect, these isolated translocations need further tissue studies to look for mosaicism and a follow up to confirm whether they are indicators of malignancy or altered immune response. This has to be explained to the patients as a part of counseling and warrants a note of precaution to the family physician. References
1. Hecht F, McCaw BK, Peakman D, Robinson A. Nonrandom occurrence of 7-14 translocations in human

Chromosomal abnormality in a single cell can be considered as one where the abnormality is seen only on one metaphase spread even when more spreads are analyzed on suspicion of the abnormality. Translocation t(7;14) was the most frequently noticed reciprocal translocation abnormality. Various implications of the effect of this t(7;14) were meiotic translocations in humans are generally nonrandom. These translocations may lead to repositioning of genetic material and in some instances can change the cell behavior or function in some unexplained manner and may lead to variable phenotypic expressions.[1] These isolated translocations may be indicators of mosaicism whereby other tissues like fibroblasts or gonads may have to be analyzed to confirm or rule out such a possibility.[2] These single cell translocations warrant the need to study the parental chromosome status to find out their nature of origin de-novo/transmitted. The present analysis revealed that 50% of such single

Table 1: Genotype and clinical presentation

S. No. 1 2 3 4 5 6 7 8 9 10 Sex F F F M M M M M M M Clinical condition BOH BOH BOH BOH BOH MR MR MR MR Hypogonadism 46,XX, t(4;21) 46,XX, t(7;14) 46,XX, t(7;14) 46,XY, t(7;14) 46, t(X;9;8) Y 46,XY, t(7;14) 46,XY, t(7;14) 46,XY, t(7;14) 46,XY, t(2;10;11) 46,XY, t(7;14) Karyotype

BOH, bad obstetric history; MR, mental retardation

Isolated cell translocations lymphocyte culture. Nature 1975;255:243. Rao VB, Kar B. Single Cell translocation, is it coincidental or causal. Indian Pediatr 1999;36:321-2. Arakaki DT, Sparkes RS. Microtechnique for culturing leucocytes from whole blood. Cytogenetics (Basel) 1963;2:57-60. Higgins MD, Palmer CG. Single cell translocation in couples with multiple spontaneous abortions. Hum Genet 1987;75:24-7. Beatty DeSana JW, Hoggard MJ, Cooledge JW. Nonrandom occurrence of 7-14 translocations in human

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6.

7.

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5.

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lymphocyte culture. Nature 1975;255:242. Welch JP, Lee CL. Nonrandom occurrence of 7-14 translocations in human lymphocyte culture. Nature 1975;255:241. Murre C, Waldermann R, Morton C, Bongiovanni K, Waldmann T, Shows T, et al. Human gamma chain genes are rearranged in leukemic T cells and map to the short arm of chromosome 7. Nature 1985;316:54952. Reddy K, Thomas I. Significance of acquired nonrandom 7; 14 translocation. Am J Med Genet 1985;22:305-10.

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