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T8m features are variable, however, some anomalies are more common than others. The severity of the phenotypes in T8m patients is not directly related to the level of mosaicism found (Riccardi 1977; Berry et al.1978; Swisshelm et al. 1981; Kurtyka et al. 1988). Several cases of similar mosaicism levels have been compared, however the patient phenotypes differ. For example, one patient had 100% trisomy 8 cells in lymphocytes and over 60% in fibroblasts with a near normal phenotype and IQ (James and Jacobs 1996). Comparatively, another patient was diagnosed with 94% trisomy 8 cells in lymphocytes and 70% in fibroblasts and had severe mental retardation and various skeletal anomalies (Jordan et al. 1998). The exact mechanism which causes the severity of phenotype in T8m patients is unknown, but believed to be associated with either the “post zygotic origin of the trisomic status” (Miller et al 1997) or dependent upon the contribution of aneuploid cells in the development of different tissues (Kurtyka et al. 1988). T8m is associated with disappearing mosaicism over time. The percentage of trisomic cells decreases in a patient when tested several months to years after the initial testing (La Marche 1967; Mark and Bier 1997). Jordan et al. in 1998 described two cases showing disappearing T8m. Patients were analyzed over an 8 and 9 year period to evaluate any change in trisomy 8 cell percentages. Both cases were shown to have a significant decrease of trisomy 8 cells in cultured lymphocytes. Kurtyka et al. (1988) also reported cases with similar disappearance of trisomy 8 cells in lymphocytes. Mark and Bier (1997) suggested the trisomic line may disappear completely if enough time has gone by. The decrease in trisomic cells has been attributed to a selective growth advantage of the normal cells (La Marche et al. 1967; Mark and Bier 1997). 4
Prenatal Testing Prenatal testing is routine for women with an increased risk for possible fetal anomalies. Testing is done on women with advanced maternal age, abnormal maternal triple screen results, or abnormal fetal results from ultrasound. Typical prenatal testing includes amniocentesis and chorionic villi sampling (CVS). Amniocentesis is usually performed at 15-17 weeks gestation. Amniotic fluid and cells are removed from the amniotic sac via a syringe through the abdomen. The amniocytes within the fluid are grown in culture and harvested for cytogenetic analysis and diagnosis. CVS is performed during the first trimester and before the amniotic sac is fully expanded in the uterine cavity (Filkins and Russo 1990). A sampling catheter is inserted into the uterine cavity vaginally. The catheter is then inserted into the chorion to collect a sample for cytogenetic testing. T8m is problematic from the standpoint of genetic counseling due to several T8m cases diagnosed in amniocytes, with only normal cells found in the aborted fetus. Also, misdiagnosis can occur when the results obtained from initial diagnosis of amniocytes are normal, and the pregnancy results in an abnormal fetus (Guichet et al. 1995; Karadima et al. 1998; Webb et al. 1998). One way to prevent misdiagnosis of T8m when suspected by abnormal ultrasound findings is to test other cells along with amniocytes, such as lymphocytes from prenatal umbilical blood (Berry et al. 1978; Guichet et al. 1995; Miller et al. 1997). The testing of additional tissues is necessary for cases involving mosaicism, since it will either confirm or negate the original diagnosis. Another cause of concern for genetic counseling is the lack of correlation between the phenotype and the amount of trisomy 8 cells present. This makes it very difficult to give a definitive prognosis 5
Page 1 and 2: TRISOMY 8 MOSAICISM: CELL CYCLE KIN
Page 3 and 4: TABLE OF CONTENTS iii Page Abstract
Page 5 and 6: Trisomy 8 INTRODUCTION Trisomy 8 (T
Page 7: proliferates and thus mosaicism res
Page 11 and 12: DNA undergoing synthesis. Once a sa
Page 13 and 14: centrifugation, aspiration, and fix
Page 15 and 16: insed with water and allowed to air
Page 17 and 18: fixative, and the centrifugation an
Page 19 and 20: FISH slide preparation Day 1 Slides
Page 21 and 22: Case Report RESULTS Amniocentesis,
Page 23 and 24: Figure 2 Trisomy 8 [46, XY, +8] Kar
Page 25 and 26: When comparing embryonic tissues, c
Page 27 and 28: Figure 4 FISH Trisomy 8 [46, XY, +8
Page 29 and 30: There was a notable difference betw
Page 31 and 32: For each tissue the metaphase and i
Page 33 and 34: Figure 6 Second Division - Cell Cyc
Page 35 and 36: Table 4. Division Rates for Normal
Page 37 and 38: Origin of Trisomy 8 cells DISCUSSIO
Page 39 and 40: original finding of La Marche in th
Page 41 and 42: Pallister Killian patients with the
Page 43 and 44: BIBLIOGRAPHY Berry AC, Mutton DE, a
Page 45: Thornberg Reeser SL and Wenger SL.

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