Results of 730 Chromosome Studies on Patients Referred for Cytogenetic Analysis at Chromosome Analysis Certer in Ubon Ratchathani University

ABSTRACT: During Febuary 2004 – June 2007, 730 individuals, ascertained due to clinical findings for cytogenetic evaluation with amniocentesis and lymphocyte culture methods, were examined by automated G – banded karyotyping. A total of 136 (19%) had an abnormal karyotype: 46 (34%) were Down syndrome whist a further 90 (66%) had other types of chromosome abnormalities. The Philadelphia chromosome or t(9q:22q) translocation is the most frequent structural abnormalities (25%). These findings suggest that cytogenetic analysis is useful in the investigations of patients referred for cytogenetic evaluation in order to confirm clinical diagnosis in patients with known cytogenetic syndrome and for prenatal diagnosis and genetic counseling.

Introduction : A chromosome abnormality reflects an abnormality of chromosome number or structure. Chromosome abnormalities can be inherited from a parent such as a translocation or be new to the individual (de novo). This is why chromosome studies are often performed on parents after a child is found to have an abnormality. Most chromosome abnormalities occur as an accident in the egg or sperm. Therefore, the abnormality is present in every cell of the body. Some abnormalities, however, can happen after conception,resulting in mosaicism(mos), where some cells have the abnormality and some do not. The karyotype can help identify chromosome abnormalities. Structural abnormalities of all 44 autosomes and the 2 sex chromosomes have been investigated. In this paper, we reported the results of 730 chromosome studies on patients referred for cytogenetic analysis at Chromosome Analysis Center in Ubon Ratchathani University.

Methodology : The mitotic chromosomes were prepared by using lymphocyte culture and amniocentesis. A whole-blood culture was incubated for 72 hrs 37 .C. The amniocentesis procedure involves in getting a small sample of amniotic fluid from around the fetus by physician. A thin needle of 21 or 22 gauge needle is inserted under ultrasound imaging guidance to aspirate the fluid. A sample of the amniotic fluid (about 15-20 cc) is then withdrawn through the needle and taken to a laboratory. These cells are allowed to grow and multiply to monolayer in a cultural flask until there are enough for the chromosome harvesting. The metaphase chromosomes were banded by GTG – banding which were performed in the manner of Seabright (1971) The 25 well – spread metaphase cells were carefully analyzed, photographed and karyotyped by automated chromosome analyzer.

Result, Discussion and Conclusion : The main results were summarized in Table 1 and Figure 1 – 10. The highest frequencies of abnormal karyotype were found among cases that were referred due to suspicion of Down syndrome (34%), and of Philadelphia chromosome in chronic myeloid leukemia or CML (25%).
     This study showed that the frequencies of chromosomal aberrations in those cases generally conform to those reported in similar studies (Muneera et al 1999). Thorough clinical search for subtle dysmorphic features should help physicians to decide on the need to request cytogenetic evaluation. Referral of cases to an experienced dysmorphologist prior to cytogenetic analysis is advisable. This will decrease the number of unnecessary referrals and enhance the referrals of cases with minimal features of chromosomal anomalies.

Table 1. The results of 730 chromosome studies on patients referred for cytogenetic analysis at Chromosome Analysis Center in UbonRatchathani University.

Methology Normal Karyotypes Abnormal Karyotypes
46,XX 194 cases
46,XY 190 cases
Culture failure 1 case
47, 47,XX or XY,+21 ;Down syndrome 3 cases
47,XX,+18 ; Edward syndrome 1 cases
47,XXY; Klinefelter syndrome 2 cases
47,XX,+13 ; Patua syndrome 1 cases
mos45,XO/47,XXX 1 cases
total 385 cases 8 cases
Lymphocyte culture
46,XX 92 cases
46,XY 112 cases
Culture failure 5 cases
Autosomal aneuploidies :
47,XX or XY,+21 ;Down syndrome 46 cases
47,XX or XY,+18 ;Edward syndrome 14 cases
47,XX or XY,+13 ;Patua syndrome 9 cases
45,XO ;Turner syndrome 6 cases
46,Xiso(Xq) 2 cases
mos45,XO/46,XXq+ 1 case
mos 45,XO/46,XO,+ marker 1 case
mos46,XX/47,XX,+18 1 case
Structural aberrations :
Philadelphia chromosome :t(9q:22q) 34 cases
46,XY,female : testicular feminization 2 cases
Unbalanced Robertsonian translocation:
- 46,XY,t(14q:21q) 1 case
- 46,XY,t(21q:21q) 1 case
Others : 10 cases
total 209 cases 128 cases
All total 730 cases

Fig.1 Down syndrome or 47,XY,+21

Fig.2 Edward syndrome or 47,XX,+18

Fig.3 Patua syndrome or 47,XX,+13

Fig.4 Klinefelter syndrome or 47,XXY

Fig.5 Philadelphia chromosome or t(9q:22q)

Fig.6 Cri du chat syndrome or 45,XX,5p-

Fig.7 Isochromosome in long arm of X-chromosome or iso(Xq) or 46,Xiso(Xq)

Fig.8 Down syndrome : D/G unbalanced Robertsonian translocation or 46,XY, t14q:21q)

Fig.9 Down syndrome : G/G unbalanced Robertsonian translocation or 46,XY,t(21q:21q)

Fig.10 Turner syndrome or 45,XO

REFFERENCES : 1.Muneera Al, Husaina, Osama K. Zakib. 1999. A Survey of 1,000 Cases Referred for Cytogenetic      Study to King Khalid University Hospital, Saudi Arabia Human Heredity 49:208-214 Grouchy J, Turleau C. 1999. Autosomal disorders; In Emery A, Rimoin, D (eds): Principles and
     Practice of Medical Genetics. New York, Churchill Livingstone 1999:247-274.
KEY WORD : chromosome studies, abnormal karyotype,UbonRatchathani univetrsity
Acknowledgments: This research is supported by the Department of Biological Science Faculty of Science UbonRatchathani University.