Ring chromosome 15 and 15qs+ mosaic: clinical and cytogenetic behaviour spanning 29 years.

A phenotypic female with mild mental retardation, minor facial anomalies, and short stature has been evaluated clinically and cytogenetically over 29 years. At age 59, she remains physically well and shows no signs of dementia. Cytogenetic analysis, performed on peripheral blood specimens on 10 occasions between 1961 and 1990, showed mosaicism with one cell line containing a large stable ring (15) chromosome and another cell line without the ring but with a 15qs+. The different cell lines remained constant. The case provides information on the natural history of the ring chromosome 15 syndrome.

Cytogenetic studies in perinatal death.

Following tissue culture cytogenetic studies were performed on tissue obtained from 136 fetuses who died in the perinatal period (98 stillbirths and 38 neonatal deaths). The gestational age of the stillbirths was evenly distributed between 20 and 40 weeks (1 was 42 weeks) while 74% of the neonatal deaths were term babies. Analyzable metaphases were obtained in 45 stillbirth specimens (46%) and 32 neonatal specimens (84%). Abnormal karyotypes were identified in 7 of the stillbirths (15.5%) and 8 of the neonatal deaths (25%) and all these were from babies with congenital anomalies identified at autopsy. Time delays were crucial to the success of culture from stillbirths, but specimens obtained from neonatal deaths could be grown successfully up to 3 days after death. Generally the placenta was more viable than other tissues, including skin, cartilage and muscle. Whereas growth was obtained in 69% of fresh unexplained stillbirths, no tissue from the macerated stillbirths grew. This is a group which may have a high abnormality rate. We recommend that if fetal assessment during pregnancy suggests a compromised fetus and there are no maternal factors to account for this, an amniocentesis be performed.

Chorionic villus sampling--short-term versus long-term culture in a subtle 2; 18 translocation.

Prenatal diagnosis on chorionic villous tissue was performed for a woman with the karyotype 46,XX,t(2;18)(q32;q12)--a subtle 'difficult' translocation. The case illustrates the necessity of good quality cytogenetics for accurate prenatal diagnosis. For chorionic villi this can be obtained only with long-term culture.

Recurrence of different mosaic structural chromosomal anomalies within a family.

We present a family in which chromosomally normal parents have had two different structurally abnormal pregnancies. These rearrangements have both been in the mosaic form with a normal cell line. Various mechanisms for this rare situation are discussed.

Classical Prader-Willi syndrome with trisomy 15(pter----q12) plus de novo variant 15p11.

We describe a boy with the classical Prader Willi syndrome (PWS), clinically, who had a chromosome abnormality not previously described in PWS. The karyotype was 47,XY,+mar, var(15)(p11). The marker was a fragment of 15 from 15pter----q12 and the variant 15p11 was de novo in origin. Overall, this karyotype contains increased 15 heterochromatin and we discuss alteration in the amount of 15 heterochromatin in PWS.

Extra embryonic/fetal karyotypic discordance during diagnostic chorionic villus sampling.

From a total of 1312 diagnostic chorionic villus samplings (CVS) there were 22 which showed discordance between the karyotype of the chorionic villi and that of the fetus. This frequency was some 20-fold higher than that reported at amniocentesis. In the majority of discordant cases, the fetal karyotype was normal while the placental karyotype was mosaic. In four cases, the placental karyotype was non-mosaic (a trisomy 16, a monosomy X, and two tetraploids) while the fetal karyotype was normal. In one case, the placenta was trisomy 18 while the fetus was mosaic. There were two 'false-negative' results where short-term methods showed only normal cells while both long-term cultures of chorionic villi and fetal cells were mosaic, in one 46,XY/47,XXY and in the other 46,XY/47,XY,+21.

Cytogenetic findings in cell lines derived from four ovarian carcinomas.

Six cell lines, established from four primary ovarian carcinomas were examined cytogenetically. The lines varied greatly in their chromosome complement. All cells from the lines were aneuploid, although one cell line contained two populations having a pseudodiploid and a pseudotetraploid modal chromosome number. Every chromosome group was involved with loss and gain of chromosomes, but some individual chromosomes were more prone to aneuploidy than others. Chromosome #6 was the most stable throughout. Structural changes gave rise to many marker chromosomes. Although most markers were random and the majority unidentifiable, some abnormalities of clonal origin were found. Deletions especially of chromosome #1, were the most common change. Further sequential studies may elicit the origin, stability, and timing of the chromosome abnormalities.

Clinical experience with 50 cases of first-trimester fetal diagnosis by chorionic biopsy.

Prenatal diagnosis by chorionic biopsy was undertaken between the eighth and 12th weeks of pregnancy in 50 patients at risk of chromosomal or genetic abnormalities. Samples from 45 patients were karyotyped. A DNA analysis for the detection of homozygous beta-thalassaemia was undertaken in five patients. The sample from one patient at risk of haemophilia in the fetus was subjected to DNA analysis after a male fetus was confirmed on karyotyping. Abnormal karyotypes were detected in four fetuses while three had homozygous beta-thalassaemia.

A male with two different familial autosomal fragile sites and a cytogenetically abnormal offspring.

During the course of routine prenatal cytogenetics, a male with 2 different autosomal fragile sites (FS) was detected. The FS were at 9p21 and 12q13 and his sister also had both fragile sites, inherited from an obligate carrier father. He was the father of a foetus with an abnormal chromosome complement 46,XY/47,XY,+frag. The origin of the fragment could not be determined.

Familial deletion.

We report a retarded male with an unbalanced karyotype 45,XY,t(8;15) (p23;q12) showing small deletion of chromosome 8(p23 leads to pter) and 15(pter leads to q12). The same chromosome complement was also present in 4 normal family members over 3 generations.

Follow-up of case of advanced survival and trisomy 18.

We have reported the results of skin culture of a girl with trisomy 18, previously reported when eleven years of age and now aged twelve-and-a-half years. There was no evidence of mosaicism.

A severely retarded 18-year-old boy with tertiary partial trisomy 14.

An 18-year-old severely mentally and physically retarded boy was found to have an unbalanced chromosome complement 47,XY, + 14q-. He had the characteristic facial dysmorphis, abnormal hands, and other features described previously in cases of partial trisomy 14, but appears to be the oldest case reported. His mother is a reciprocal translocation carrier, and lack of other carriers in the family is noteworthy.

An abnormal dicentric X chromosome in a patient with short stature and gonadal dysgenesis.

A 16 year-old girl with short stature and gonadal dysgenesis was found to have a chromosomal complement consisting of 46,X,dic(X) (qter yields p22::p22 yields qter). When comparing her clinical features with 7 other cases who appeared to have precisely the same abnormal dicentric X, it was found that even though the percent of 45,X cells present varied considerably from patient to patient, these patients were remarkably similar and the stigmata, of Turner's syndrome were minimal in this group as a whole.