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Indian Journal of Human Genetics, Vol. 11, No. 2, May-August, 2005, pp. 59-60 Editorial Chromosomal Variants and Genetic Diseases Rao VB, Ghosh K Institute of Immunohaematology (ICMR), K.E.M Hospital Campus, Parel, Mumbai, India
Code Number: hg05015 Genetic diseases, also called hereditary diseases, are the most burdensome of all human afflictions. Genetic diseases are determined at conception but can be expressed at any time of life. Roughly, 1 out of 20 children admitted to hospital has disorder which is entirely genetic in origin and such disorders account for about one out of ten childhood deaths in hospital. A number of surveys have indicated that at least 1 out of 50 newborn has a major congenital abnormality and 1 out of 200 has a major chromosomal abnormality.[1] This issue of the journal documents several such anomalies as isolated case reports. The incidence of chromosomal abnormalities is many times greater in spontaneous abortions than among live births. In early spontaneous abortions over 50% have a chromosomal abnormality; however, 10-15% chromosomal abnormalities reported in couples with recurrent spontaneous abortions. In case of stillbirths and neonatal deaths between 6 and 7% have a chromosomal abnormality. This indicates that the majority of chromosomal abnormalities present at conception are lethal in early pregnancy or later and only a small proportion of all such abnormalities is exhibited in live births. Advancement in cytogenetic technology using fluorescence in situ hybridization (FISH) helped us to detect microchromosomal rearrangements and low-grade mosaicism. There are three types of chromosomal variations; mosaicism, heteromorphism, single cell translocations commonly seen in routine chromosomal analysis. There is one article in this issue (Dubey et al.), where authors reported only 2% of chromosomal abnormality and few cases with mosaicism in couples with recurrent spontaneous abortions (RSA) using conventional methods. Recently a high frequency (50%) of chromosomal mosaicism was reported in couples with RSA using a panel of probes in FISH study.[2] Hence, there is a need to rule out mosaicism using FISH in all such patients for appropriate counselling. The authors′ observations on chromosomal variants such as pericentric inversion of chromosome 9, 9qh+, 1qh+, 15p+ were interesting. Earlier these variations were considered to be chromosomal polymorphisms and so far clinical correlation of these polymorphisms has not been established. These variations always put genetic counsellors in dilemma. However, in recent years several studies have shown that repeated sequences located on the same chromosome at a distance of a few mega bases, predispose to homologous unequal recombination leading to both chromosome microrearrangements, i.e. deletions, duplications and inversions.[3] Hence, the detailed studies on heterochromatin are important to know their role in genetic diseases. The second common heteromorphism in cytogenetic screening is nucleolus-organizing regions on acrocentric chromosomes and chromosome 15 reported to be frequently involved. The NORs banding method is routinely used to confirm the NORs stalks but this method always may not detect all NORs and for cytogenecists it is difficult to differentiate the additions on acrocentrics. During human genome project one sequence is found to be hybridized with NOR region and now the clone is available in PAC (dJ1174A5). Recently, we have confirmed 15p+ as NOR using the same probe.[4] The third chromosomal variation commonly seen in cytogenetic screening is single cell translocations. The t(7;14) is reported to be commonly involved in patients bad obsteric history, children with dysmorphic features[5] and the clinical correlation has not been etablished. However, the other single translocations reported in one of the paper in this issue (Rema Devi and Sayee) are interesting. In such cases the conventional cytogenetic method using G-banding is not enough to rule out the mosaicism and FISH studies in peripheral blood and tissue is important to decide the mosaicism. In conclusion, the chromosomal variations including single cell translocations, numerical anomalies, single cell chimerism, chromosomal heteromorphism plays an important role in genetic diagnosis and these variations should be studied in detail using FISH and molecular methods, which helps in better management of the disease.should be studied in detail using FISH and molecular methods, which helps in better management of the disease. References
Copyright 2005 - Indian Journal of Human Genetics |
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