Significance of a prenatally diagnosed del(10)(q23).

Structural chromosome mosaicism is rare. We report a case of prenatal mosaicism for a deletion of chromosome 10(q23). To our knowledge, there are only three reports of prenatally diagnosed cases of del(10)(q23). Two of these cases were due to an inherited fragile site. In the present case amniocentesis revealed 46,XY,del(10)(q23)[9]/46,XY[45]. Follow-up chromosome analysis of peripheral blood and placental tissue from a phenotypically normal liveborn male revealed the del(10)(q23) in only 3/100 blood cells grown in low-folate medium. It appears that prenatally diagnosed deleted (10q) mosaicism represents culture artifact and is not clinically significant.

Prenatal diagnosis of trisomy 4 mosaicism.

Trisomy 4 mosaicism is rare. To our knowledge only two cases of prenatally diagnosed trisomy 4 mosaicism have been reported. One case resulted in a normal liveborn male, the other resulted in an abnormal liveborn female. The karyotype of our case at the time of amniocentesis was 47,XY,+4[3]/ 46,XY[33] and resulted in a normal liveborn male. FISH analysis using an alpha satellite chromosome 4 probe was performed to confirm the cytogenetic findings. Follow-up chromosome analysis of cord blood, peripheral blood, foreskin, and umbilical cord fibroblasts showed a normal 46,XY male karyotype in all cells. FISH analysis of cord blood, umbilical cord fibroblasts, and amniotic fluid cells demonstrated two signals in 246 nuclei (i.e., 46,XY) and three signals in six nuclei (i.e., 47,XY,+4). Here we describe the present case of trisomy 4 mosaicism, the literature is reviewed, and the significance of this finding is discussed.

Mosaicism with a normal cell line and an unbalanced structural rearrangement.

Mosaicism with a normal cell line (N) and an unbalanced autosomal structural rearrangement (UASR) is rare. This report describes a case of a newborn female with a karyotype of 46,XX,der(4)t(4;15)(q35;q22)/46,XX. Molecular cytogenetic analysis confirmed the origin of the derivative chromosome 4. Here we discuss this case as well as other cases of mosaic karyotypes involving N/UASR.

Prenatal diagnosis of low level trisomy 15 mosaicism: review of the literature.

Low level chromosome mosaicism found at amniocentesis is problematic for clinicians and patients. We report prenatal diagnosis of a fetus with a rare karyotype of 47,XX, + 15/46,XX. Second trimester amniocentesis was performed for advanced maternal age. Fetal ultrasound revealed a hypoplastic right ventricle and intrauterine growth retardation (IUGR). The rest of the fetal anatomy was within normal limits. A mosaic karyotype of 47,XX, + 15/46,XX was observed. The couple interrupted the pregnancy at 19 weeks by dilation and suction evacuation. Careful evaluation of multiple pieces of fetal parts and placenta revealed one abnormal finding: a single umbilical artery. Cytogenetic metaphase and fluorescent in situ hybridization (FISH) interphase analyses of cells from fetal lung, heart, placenta, and skin revealed the presence of the trisomic line in all tissues. Molecular analysis demonstrated that the origin of the extra chromosome 15 was maternal, the error most likely occurred in meiosis I and the diploid line was of biparental inheritance. This case report discusses the associated findings in this fetus and reviews the literature describing other cases of mosaic trisomy 15.

Infant with mos45,x/46,XY/47,XYY/48,XYYY: genetic and clinical findings.

We describe an infant with mos45,X/46,XY/47,XYY/48,XYYY who presented with ambiguous genitalia. Her phenotype was also remarkable for minor ear and eye anomalies and coarctation of the aorta with bicuspid aortic valve. Laparoscopy revealed bilateral Fallopian tubes and a left infantile testis with epididymis. Chromosomal analyses of blood, skin, aorta, right Fallopian tube, and left gonadal tissue showed mos45,X/46,XY/47,XYY/48,XYYY. The 46,XY cell line was identified with routine trypsin-Giemsa banding only in cultured cells from an aortic biopsy. Fluorescence in-situ hybridization (FISH) was utilized to identify the presence of 46,XY cells in other tissues. The clinical manifestations of this patient are discussed and compared with those of similar cases of Y chromosome aneuploidy. To our knowledge, this is the first report of a patient with this unusual karyotype.

Cytogenetic analysis of tissues from patients with familial paragangliomas of the head and neck.

BACKGROUND: Paragangliomas of the head and neck are slow-growing tumors that originate from neural crest cells. Between 7% and 9% of these tumors have a familial occurrence. The suspected gene for familial paragangliomas (FP) is transmitted with an autosomal dominant mode of inheritance with incomplete penetrance, and appears to exhibit genomic imprinting. It has been demonstrated by family studies that individuals who inherit the gene(s) from their father will develop the disease. Through linkage analysis, the gene(s) for FP has been postulated to be located on the long arm of chromosome 11. The discovery of many different genes has been elucidated through the cytogenetic analysis of affected individuals who carry specific chromosome aberrations. This project was designed to look for chromosome abnormalities in several second-generation family members to further assist in the localization of the gene(s) for FP. METHODS: This study involved the cytogenetic evaluation of lymphocytes, fibroblasts, and tumor cells of several second-generation family members from a three-generation family with FP of the head and neck to look for chromosome abnormalities generally, and for abnormalities of chromosome 11 specifically. Standard cytogenetic techniques were used for lymphocyte and fibroblast cultures. Tumor cells were cultured in a collagen matrix with F12 medium supplemented with 3% L-glutamine and 10% fetal calf serum. RESULTS: There were no detectable abnormalities of chromosome 11 in any of the cells. However, nonrandom abnormalities of chromosomes 5 and 7 were seen in some of the tumor cells of one FP patient. To our knowledge, this is the first article which demonstrated the ability to successfully culture FP of the head and neck.

Postnatal confirmation of prenatally diagnosed trisomy 16 mosaicism in two phenotypically abnormal liveborns.

Two phenotypically abnormal liveborns in whom trisomy 16 mosaicism was diagnosed prenatally by amniocentesis are described. Analysis of a percutaneous umbilical blood sample in one case revealed a normal chromosomal complement. Ultrasound examinations performed at the time of amniocentesis were normal. Serial sonography during the late second and third trimesters demonstrated progressive intrauterine growth retardation (IUGR) in both fetuses and a cardiac defect in one. At birth, both infants had dysmorphic features and multiple congenital anomalies. Trisomy 16 mosaicism was confirmed postnatally in both infants in skin fibroblasts; however, peripheral blood samples contained only chromosomally normal cells. The two mosaic trisomy 16 cases described in this report, together with the five confirmed cases reported previously, demonstrate the need for caution in the counselling of patients when trisomy 16 mosaicism is diagnosed prenatally in amniotic fluid samples. Such cases potentially can result in the birth of dysmorphic infants with significant birth defects, growth retardation, and possible developmental disabilities.

A rare inherited euchromatic heteromorphism on chromosome 1.

Extra genetic material that is euchromatic is generally regarded to be associated with phenotypic abnormalities. However, recent studies suggest that this is not always the case. Chromosome analysis was performed on amniotic fluid cells from a 37-year-old phenotypically normal patient referred for advanced maternal age. All the cells analysed showed a karyotype of 46,XY,1p+. The 1p+ chromosome had extra genetic material of uncertain origin in chromosome band region 1p21-->31. Chromosome analysis on the father revealed a normal 46,XY male karyotype. The mother's karyotype showed the same 1p+ chromosome. C and Q banding, as well as silver staining studies, in both the mother and the fetus support the interpretation that the extra chromosomal material was euchromatic in nature. This 1p+ chromosome may be characterized as a euchromatic heteromorphism. Euchromatic heteromorphisms not associated with phenotypic abnormalities have been reported for chromosomes 9 and 16. To the best of our knowledge, this is the first report involving this type of cytogenetic anomaly on chromosome number 1 in a phenotypically normal mother and infant.

Simultaneous expression of the rare and common fragile sites on the X chromosome.

The fragile X [fra(X)] syndrome is the most common inherited form of X-linked mental retardation and is associated with a rare folate sensitive fragile site on the X chromosome at band Xq27.3. Recently, a common fragile site located at chromosome band Xq27.2 was delineated (Sutherland & Baker 1990). In order to confirm the previous findings and to further investigate the conditions required for induction of both types of fragile sites, we studied the use of four experimental protocols. Samples from a control male, two fra(X) males and a fra(X) carrier female were studied. Both common and rare fragile sites were seen in the samples from the fra(X) subjects. Up to 4% of cells showed both common and rare fragile sites on the same X chromosome at the 500 band level. The rare and common fragile sites on the X chromosome could be clearly distinguished. From 1 to 3% of the control cells exhibited the common fragile site, while none exhibited the rare fragile site. These protocols should be useful in resolving questionable fra(X) syndrome diagnoses.

Cytogenetic analysis of head and neck carcinomas.

Ten primary squamous cell carcinomas (SCC) of the head and neck were evaluated cytogenetically after 10-14 days of in vitro culture. Addition of 3% L-glutamine was essential for consistent epithelial growth of these carcinomas. Outgrowth of cells from tissue explants contained a mixture of chromosomally normal and abnormal cells; the abnormal cells had extensive changes including translocations, marker chromosomes, inversions, deletions, and duplications. In addition, all carcinomas contained cells with pulverization and double minute chromosomes (dmin). Chromosomes 11, 13, and 14 had "hotspots" of rearrangements.

Monozygotic twins with trisomy 18: a report of discordant phenotype.

The predicted incidence of liveborn monozygotic trisomy 18 twins is one per million births. The first case of liveborn monozygotic trisomy 18 twins was reported in 1989 and we report a second case in which striking phenotypic discordance existed. The probability of monozygotic trisomy 18 twinning and the mechanisms for phenotypic discordance in trisomic twins is discussed.

Chromosomal analysis of recurrent laryngeal papillomas.

Recurrent laryngeal papillomas are tumors believed to be induced by human papillomaviruses. Severity of this disease varies due to the unpredictability of clinical remissions and recurrences. However, the severity of the disease does not affect the classification of these tumors as benign, and the rate of spontaneous conversion of recurrent laryngeal papillomas to carcinomas is very low. Laryngeal papillomas from six patients were evaluated cytogenetically after short-term culture. All six specimens were chromosomally normal, consistent with their classification as benign tumors with a low rate of malignant conversion. The presence of human papillomaviruses has no detectable effect on the chromosomes of these tumors.

Persistent chromosome damage induced by localized radiotherapy for lymphoma.

A fibroblast culture was established from a lymph node biopsy of a patient with non-Hodgkin lymphoma, 9 months after chemotherapy and intensive therapeutic x-irradiation of the area. In contrast with blood and bone marrow, which were chromosomally normal, all cells of the lymph node were chromosomally abnormal, with numerous clones having multiple structural abnormalities. Numerical abnormalities (trisomies and monosomies) were not found. Structural abnormalities included translocations, terminal deletions, and pericentric inversions, with an excess of centromeric breakpoints being the only apparent deviation from a random distribution of breakpoints. None of the rearrangements associated with malignant lymphoma were seen, indicating that the chromosome abnormalities in the lymph stroma were radiation-associated, not disease-associated. These acquired changes may be a cause of additional malignant transformation.

Diagnostic applications of H-Y serology: H-Y negative phenotype in cells from 45,X/46,XY fetus with testes.

Sexual dysmorphism should be considered likely in cases in which H-Y- phenotype and XY complement are found together. In the case described here, a pregnancy was terminated at nineteen weeks of gestation after 45,X and 46,XY cell lines were detected among cultured amniocytes. The fetus was a male with hypospadias and intraabdominal testes containing irregular tubules and hyperplastic interstitium. Cultured skin fibroblasts, containing 45,X and 46,XY lines in ratio of 18:2, were typed H-Y antigen negative. This underscores the danger of predicting gonadal type on the basis of somatic H-Y phenotype.