Cytogenetics at the University of Cape Town: A 45-year journey.

This article is a brief record of the cytogenetics laboratory from its birth in 1971, under the auspices of the University of Cape Town, throughout its development within the Department of Human Genetics, under the leadership of Professor Peter Beighton, to its present position at Groote Schuur Hospital, as a multidisciplinary unit run by the National Health Laboratory Service.

Deletion of chromosome 13 in Moebius syndrome.

A girl aged 2 1/2 years with Moebius syndrome was found to have a deletion of band q12.2 in chromosome 13 (46,XX,del(13)(q12.2]. This is the second report concerning involvement of chromosome 13q and Moebius syndrome. The observation raises the possibility that a gene responsible for Moebius syndrome is located in this region of chromosome 13.

Confirmation of a balanced chromosomal translocation using molecular techniques.

Investigation of a couple, who had produced three babies with cri du chat syndrome, showed initially that the mother had an apparent deletion of chromosome 5. It seemed likely that she had a balanced chromosomal translocation but it proved impossible to detect the second chromosome involved using routine cytogenetic methods. Molecular techniques using quantitative hybridization dosage studies were performed and these showed that the mother had a double dose of DNA in the suspected deleted area of chromosome 5. Further studies, using in situ hybridization techniques, revealed that the missing segment of chromosome 5 had translocated onto the short arms of a C group chromosome and further analysis of prometaphase chromosomes showed the presence of a balanced translocation, 46,XY,t(5;9)(5qter----5p14.1::9p22----9pter;9 qter----9p22::5p14.1----5pter). As a result of these findings, it was possible to offer prenatal diagnosis to the patient in future pregnancies, by detecting the presence of a balanced or unbalanced translocation in the fetus using molecular and cytogenetic techniques.

Partial trisomy 9--further delineation of the phenotype.

A patient with partial trisomy 9 (47,XX,+9pter----q22.1) had bilateral cleft lip and cleft palate, enophthalmos, severe micrognathia, small, apparently low-set ears, and dislocatable knees. The phenotypic findings are compared with those of other documented cases of total trisomy 9.

Cyclopia as a result of an unbalanced familial translocation, rcp(7;18)(q34;q21)

One fetus is described with cyclopia and associated abnormalities as a result of an unbalanced translocation involving chromosomes 7 and 18 [46XX,del 7, rcp(7;18)(q34;21)]. The parents had had a previous infant described as having possible holoprosencephaly, but no medical records were available to substantiate this description.

Tricho-rhino-phalangeal syndrome without exostoses, wih an interstitial deletion of 8q23.

We report on a patient with the Tricho-Rhino-Phalangeal syndrome (TRPS) with normal mentation, without exostoses and with a partial microdeletion of 8q23. Although she had the phenotypic characteristics of TRPS Type I, karyotypic analysis demonstrated the 8q-microdeletion usually associated with TRPS Type II, in which exostoses are present. Our patient represents the second reported instance of this phenotypic chromosomal association and provides further evidence for homogeneity of the TRPS.

Ultrasound examination before amniocentesis and success of culture in genetic referrals. Six years' experience in Cape Town.

Our experience in Cape Town shows that ultrasound examination is of great benefit when amniocentesis is performed to obtain amniotic fluid cells for metaphase plates from patients at risk of carrying a fetus with a genetic disorder. Data taken over a period of 6 years show that the number of blood-contaminated fluid specimens decreases significantly when patients are scanned before amniocentesis is performed. The presence of blood in the fluid increases the possibility that cells will not grow in culture. There was no evidence to suggest that ultrasound examination inhibited amniotic fluid cell growth in culture.

The fragile X chromosome in a large Indian kindred.

A large Indian kindred in which the fragile X chromosome is segregating has been investigated in Cape Town. Eight male hemizygotes and four female heterozygotes were mentally retarded. There is suggestive evidence that one deceased male of reportedly normal intelligence may have been a hemizygote. The existence of the fragile X syndrome in a number of different ethnic groups supports the contention that the gene controlling the phenotype and the fragile site are the same, or at least overlap.

The results of chromosome examinations in an institution for mental retardates in the Cape Province.

The chromosomal status of 720 patients in a large hospital for mental retardates in the Cape Province is reported. Chromosomes 21 and X were involved in 127 and 7 patients respectively, while other autosomes were implicated in 14 patients. Chromosomes abnormalities were therefore noted in 20,5% of patients. Details are given of the ages and sexes of the patients and of the structural chromosome anomalies.

Down syndrome in the Cape Peninsula and the value of amniocentesis as a preventive measure.

The increase in the incidence of babies with Down syndrome born to women of advanced maternal age has been well documented. Similarly, the social and financial implications of a decision to institutionalize or to keep the children at home have also been well covered in the literature. A 3-year study of this problem included babies with Down syndrome who were born in the Cape Peninsula hospitals, referred to the Department of Human Genetics, University of Cape Town, and proved chromosomally to have trisomy-21. The findings are presented and discussed.

Ultrasound examination before amniocentesis. Its effect on cell culture for cytogenetic studies.

In order to obtain metaphases plates from amniotic fluid cells for chromosome analysis, amniocentesis is performed on patients who are at risk of carrying a fetus with genetic disorders. Ultrasound examination is routinely done before amniocentesis as an aid to the latter procedure and to obtain clinical data concerning the fetus. Speculation that ultrasound examination would reduce the number of blood-stained taps obtained at amniocentesis and maybe also inhibit the growth of amniotic fluid cells in culture is discussed, based on findings in this laboratory over a 3-year period.

The implications of detecting an extra metacentric microchromosome on amniotic fluid cell culture.

A patient was referred for amniotic fluid cell culture because of advanced maternal age. A decisional dilemma presented itself as a result of the detection of a metacentric bisatellited microchromosome (47,XX + marker) in the amniotic fluid cell culture. The decision whether to terminate the pregnancy had to be considered because the literature revealed a number of cases of an extra marker in patients with single or multiple congenital abnormalities, although other patients with a similar marker were phenotypically completely normal. The finding of an identical marker chromosome in the phenotypically normal mother and two of her off-spring favoured the continuation of the pregnancy. It would appear as if this is the first reported case in which a familial marker chromosome was detected prenatally and the pregnancy permitted to continue to term with the birth of a normal infant.

Antenatal diagnosis in practice.

Over a period of 5 years, 434 women at risk of having abnormal babies have had antenatal daignostic tests carried out during the first half of their pregnancy by the laboratories of the Department of Human Genetics, University of Cape Town. From these investigations, it was predicted that 13 fetuses had chromosomal abnormalities, 6 had severe central nervous system defects and 4 had autosomal recessive metabolic disorders. In addition, 4 cases with X-linked recessive traits were monitored and 3 male fetuses were recognized. Affected pregnancies were terminated except for 1 with a fetal sex-linked disorder where the parents revoked their original decision. The diagnosis was confirmed by fetal autopsies in all cases except 4 (2 spontaneous abortions and 2 out-of-town terminations). There was only 1 case where culture failed and the pregnancy went to term with the birth of a baby with Down syndrome. Antenatal diagnosis is now an important part of normal clinical practice. The fact that the fetal abnormalities were recognized in 6% of pregnancies is justification for the use of this procedure.