Prenatal diagnosis of ring chromosome 6 in a fetus with hydrocephalus

A patient with ring chromosome 6/monosomy 6 mosaicism is presented. At 25 weeks' gestation, ultrasound examination demonstrated fetal hydrocephalus. Amniocentesis was performed. The fetal karyotype was 45,XY,-6/ 45,XY,-6,+f/46,XY,r(6)(p25q27). Delivery of this male infant was by Caesarean section at 37 weeks' gestation. The karyotype in peripheral blood lymphocytes was 46,XY,r(6)(p25q27) with no indications of mosaicism. The infant had hydrocephalus which required treatment with a ventriculoperitoneal shunt at 22 days of age. He had no other obvious serious congenital anomalies. By 17 months he had developed microcephaly, seizures, severe bilateral hearing loss, and global development delay. This patient provides information regarding phenotypic variability of ring chromosome 6 and also reinforces the importance of offering amniocentesis if fetal hydrocephalus is detected as an isolated anomaly.     

A cytogenetic survey of 200 unclassifiable mentally retarded children with congenital anomalies and 200 normal controls

A cytogenetic survey was carried out on 200 patients with mental retardation and multiple congenital anomalies, and on 200 normal adult controls. Patients with a known syndrome were excluded from the survey. Chromosome analyses were carried out on 'blind-coded' slides using the ASG banding technique as the routine stain. After the initial analyses (at least 15 cells per person) the slides were decoded, destained and reused for C and Q band polymorphism studies. Five major chromosome abnormalities were detected in the patient group during the survey. They included three patients with de novo, apparently balanced, reciprocal translocations, karyotypes 46,XY,rcp(3;16)(q21;p12); 46,XX,rcp(5;8)(p15;q22); and 46,XX,rcp(5;12)(p11;q24); one with karyotype 47,XX,+mar and one with karyotype 46,XX,der(13),t(13;?)(q34;?). One additional patient whose karyotype in lymphocytes was 46,XX,inv(9)(p11;q13) was found to have a mosaic karyotype 46,XX,inv(9)(p11;q13)/46,XX,inv(9) (p11;q13), der(12),t(12;?)p13;?) in cultured skin fibroblasts. None of the 200 controls had a major chromosome abnormality. From the combined results of this and previous surveys it is now apparent that about 6.2% of the unclassifiable mentally retarded patients with three or more congenital anomalies and about 0.7% of the controls reveal major chromosome abnormalities.     

2q21-qter trisomy in hepatoblastoma

Cytogenetic findings and fluorescens in situ hybridization results of a hepatoblastoma of a boy of two and half years of age are presented. Cytogenetic analysis and fluorescens in situ hybridization technique were performed using tumor tissue obtained by biopsy. The direct culture was harvested after 16 hour colcemid treatment. The results of G-banding were as follows: 47,XY,add(4) (q26),-9,+20. There were considerable variation in the degree of condensation and hence in the number of visible G-bands both between metaphases and between homologous chromosomes in the same metaphases. Fluorescens in situ hybridisation were carried out by whole chromosome painting probes: 2,3,4, and 20. The karyotype of the malignant cells was adjusted accordingly: 47,XY,der(4)(q35),dir ins(9;2)(p22;q?21q?25),+20. The results confirm the most common primary chromosome abnormalities in hepatoblastoma are the following: trisomy 2, trisomy 20 and 4q structural rearrangement. Fluorescens in situ hybridization confirms the importance of trisomy 2q21-qter in hepatoblastoma. Authors recommend the use of fluorescens in situ hybridization to correct any tumor karyotype with difficult or ambiguous chromosome morphology.     

Complete and partial XY sex reversal associated with terminal deletion of 10q: report of 2 cases and literature review

We describe 2 karyotypically male infants with terminal deletion of 10q and mental retardation, multiple phenotypic anomalies and abnormal genitalia. One [karyotype 46,XY, del(10)(q26.1)] had female external genitalia; the other [karyotype 46,XY,-10,+der(10)t (10;16)(q26.2;q21)] had an intersex phenotype. Of 8 males previously reported with terminal 10q deletion as the major or only cytogenetic abnormality, 2 had an intersex phenotype, and the others all had combinations of cryptorchidism, micropenis, and hypospadias. Terminal 10q deletions appear to be strongly associated with abnormal male genital development, and should be specifically searched for in the cytogenetic workup of such cases.     

Der(22)t(11;22) resulting from a paternal de novo translocation, adjacent 1 segregation, and maternal heterodisomy of chromosome 22

The t(11;22) (q23;q11) translocation is the most frequently identified familial reciprocal translocation in humans. In translocation carriers, 3:1 meiotic segregation with tertiary trisomy can occur resulting in abnormal progeny with the der(22) as the supernumary chromosome. Affected children have a distinct phenotype with multiple anomalies and severe mental retardation. We have identified a child with developmental delay and multiple anomalies consistent with the der(22) phenotype. Cytogenetic analysis showed an abnormal chromosome complement of 47,XX,+der(22)t(11;22)(q23; q11) in all 50 cells analysed. FISH analysis using chromosome 11 and 22 painting probes showed a pattern consistent with a reciprocal translocation of the distal bands 11q23 and 22q11 respectively. Parental karyotypes were normal. RFLP analysis of locus D22S43, which maps above the t(11;22) breakpoint, showed that the der(22) was paternal in origin and indicated that the normal chromosomes 22 were the probable result of maternal heterodisomy. RFLP analysis of locus D22S94, which maps below the t(11;22) breakpoint, also suggested that both normal chromosomes 22 of the child represented the two maternal homologues. Non-paternity was excluded through the analysis of 10 microsatellite markers distributed on 10 different chromosomes and three VNTRs on three different chromosomes. To the best of our knowledge, this is the first reported case of a patient with an abnormal karyotype resulting from a de novo translocation in the paternal germline with probable unbalanced adjacent 1 segregation and maternal non-disjunction of chromosome 22 in meiosis I.     

Significance of abnormalities of chromosomes 5 and 8 in chondroblastoma

Tumor specific chromosomal abnormalities have been identified in several histologic subtypes of benign and malignant bone tumors. These anomalies have proven to be useful diagnostically. Characterization of recurrent chromosomal abnormalities also has provided direction for molecular investigations of pathogenetically important genes. Cytogenetic reports of chondroblastoma, a rare benign bone tumor, are few. Cytogenetic analysis of a benign and a malignant chondroblastoma in this study revealed the following abnormal chromosomal complements: 47,XY,+5,t(5;5)(p10;q10) and 45, XY,del(2)(p23),del(3)(q23q27),dup(8)(q12q21.), del(11) (q14q23), -13, add (17) (q25) x 2, respectively. Although a specific chromosomal abnormality has not yet emerged for chondroblastoma, abnormalities of chromosomes 5 and 8 have been reported previously in this neoplasm, suggesting preferential involvement of these two chromosomes.     

Prenatal detection of short arm deletion and isochromosome 18 formation investigated by molecular techniques

A patient was referred for amniocentesis because of advanced maternal age and polyhydramnios. The fetal karyotype was a mosaic 46,XX,del(18)(p11.1)/46,XX,-18,+i(18q)de novo. The deletion appeared to encompass the whole short arm as evidenced by G banding and in situ hybridisation. However, telomere sequences were found on both ends of the deleted chromosome as well as the isochromosome. The normal 18 and the isochromosome showed more alphoid sequences than the del(18). Subsequent passages of the cell lines showed an increase in the frequency of the isochromosome from 20% to about 30%. Possible mechanisms are discussed.     

Granulocyte colony-stimulating factor (G-CSF) mediated mobilization of leukemic cells in Philadelphia chromosome positive acute lymphoblastic leukemia expressing myeloid antigens (my+Ph+ALL)

We report a male infant who has impaired penile development, hypospadias, and mild developmental delay with a 46,XY,t(1;18)(q32.1;q22.1) karyotype. Fluorescent in situ hybridization (FISH) was performed to more precisely map the translocation breakpoint. The translocation breakpoint maps to a region that has been implicated in genitourinary malformations in the 18q- syndrome. This case report suggests that a gene involved in genitourinary development maps at or near the chromosome 18 translocation breakpoint.     

Prenatal diagnosis of supernumerary chromosome derivative (22) due to maternal balanced translocation in association with diaphragmatic hernia: a case report

An aneuploid fetus was detected prenatally by cordocentesis at 27 weeks' gestation following ultrasonographic diagnosis of severe fetal growth retardation and a large diaphragmatic hernia. The fetal karyotype was revealed to be 47,XX,der(22)t(11;22)(q23.3;q11.2) after parental bloods confirmed a balanced reciprocal translocation in the mother. Approximately 85 cases with an unbalanced karyotype 47,XX(or XY),+der(22),t(11;22) due to 3:1 meiotic disjunction in the parental translocation carrier have been reported in the world literature and only one of them was diagnosed prenatally. This is the first detailed case report of a supernumerary derivative (22) chromosome abnormality diagnosed prenatally in association with diaphragmatic hernia.     

Low-level mosaicism for both trisomy 15 and monosomy-X in amniotic fluid cells confirmed in fetal tissues

We report here a case of true fetal mosaicism for both trisomy 15 and monosomy-X; the aberrant cell lines were initially detected at amniocentesis as low-level mosaicism (trisomy 15) and multiple-cell pseudo-mosaicism (monosomy-X). In the fetal lymphocytes, only metaphases with a normal chromosome complement were observed. After termination of the pregnancy, various fetal biopsies revealed both trisomy 15 and monosomy-X mosaicism, whereas, at autopsy, no external or internal abnormalities could be detected in the fetus. The karyotype can be described as 45,X[15]/47,XY,+15[3]/46,XY[27]. Our results implicate that an additional amniocentesis could be more helpful than fetal blood sampling in predicting the fetal karyotype after diagnosis of chromosome mosaicism at amniocentesis.     

Constitutional mosaicism for a chromosome 9 inversion resulting in recombinant aneusomy in an offspring

We report on a case of constitutional mosaicism for a large pericentric inversion of chromosome 9 in a man whose daughter had recombinant aneusomy resulting in partial 9q duplication and partial 9p deletion. At age 6 months, the girl was evaluated because of congenital anomalies [corrected] and developmental delay. Chromosomal analysis on this infant showed a derivative chromosome 9 which was later determined to be a recombinant chromosome with trisomy of 9q34.1-->qter and monosomy of pter-->9p24. Chromosomal analysis in her father showed the presence of two cell lines; 75% of lymphocytes had a 46,XY pattern, and 25% had a 46,XY,inv(9)(p24q34.1) karyotype. The infant's physical findings represent a composite of the reported cases of both trisomy 9q34.1-->qter and monosomy pter-->9p24. The infant's father was phenotypically and cognitively normal. This case broadens the spectrum of reported cases of mosaicism for an autosomal structural rearrangement generating unbalanced gametes, and further supports the tenet that constitutional mosaicism has clinical relevance for genetic counseling.     

Mechanical environment associated with rotator cuff tears

The patient is a 12-year-old boy with acute mixed lineage leukemia (AMLL) and with a rare karyotype of trisomy 6. He was referred to our hospital with gingival swelling, bleeding at the conjunctiva and huge hepatosplenomegaly. Complete blood count revealed leukocytosis with 79% blasts, anemia and thrombocytopenia. Bone marrow examination revealed 82.5% blasts which were morphologically judged as M1 according to the French-American-British classification. Immunophenotyping of leukemic cells showed the presence of CD2, CD7, CD19 and CD13 antigens, suggesting the diagnosis of AMLL. Cytogenetic analysis revealed a single abnormal karyotype of 47,XY,+6,add(15)(q22) which was successfully detected by fluorescence in situ hybridization (FISH) with the probe mapping at the alpha-satellite region of chromosome 6. Although the patient was treated with several chemotherapy regimens, he could not achieve complete remission and he died of progressive disease 11 months after admission. Fluorescence in situ hybridization analysis was very informative in assessing the residual leukemic cells in interphase during his clinical course.     

Of abscission and other breakthroughs

Plexiform fibrohistiocytic tumors are rare lesions of proposed myofibroblastic origin occurring primarily in infants and children. There is a characteristic biphasic histology comprised of both fibroblastic and histiocyte-like components. These tumors tend to be locally aggressive with prognosis dependent on completeness of resection. A previous cytogenetic case report of this tumor described a stemline clone with a karyotype of 46,XY,-6,-8, del(4)(q25q31),del(20)(q11.2),+der(8)t(8;?) (p22;?),+mar. We report a different cytogenetic finding in another plexiform fibrohistiocytic tumor which demonstrated a simpler karyotype of 46,XY,t(4;15)(q21;q15). The implications of cytogenetic heterogeneity in fibroblastic tumors is briefly discussed.     

Are duodenal ulcer seasonal fluctuations paralleled by seasonal changes in 24-hour gastric acidity and Helicobacter pylori infection?

Short-term cultures from two histologically benign chemodectomas, one from the carotid body and one from the vagal nerve, were analyzed cytogenetically. The former had a small abnormal clone with the karyotype 46,XX,t(3;19)(q21;q13),t(12;15) (p13;q12-14), whereas the majority of the cells from the latter tumor displayed two related abnormal clones: 46,XY,i(I)(q10)/ 46,iderm,add(2)(q37). The findings add to the evidence that chemodectomas are heterogeneous neoplasms and suggest that the heterogeneity may possibly be associated with the site of origin.     

Metaphase analysis of metanephric adenoma reveals chromosome Y loss with chromosome 7 and 17 gain

A 61-year-old man underwent wedge excision of a 3-cm right renal metanephric adenoma. This recently recognized tumor has been considered benign, although no genetic studies have been reported. Metaphase analysis demonstrated a 47,X,-Y,+7,+17 karyotype. These results are consistent with a clonal neoplastic disorder.     

The t(14;18) in a patient with de novo acute lymphoblastic leukemia is associated with t(8;9)

Cytogenetic analysis of a bone marrow aspirate from a patient with acute lymphoblastic leukemia (ALL) revealed the presence of a complex karyotype containing the translocation, t(14;18)(q32;q21). Further investigations using fluorescence in situ hybridization (FISH) allowed the characterization of an additional translocation, t(8;9)(q24;p1?). The association of t(14;18)(q32;q21) and t(8;9)(q24;p13) has recently been described in two patients with de novo ALL (Nacheva et al. Blood 1993;82:231-240) and this report supports these findings.     

Hypospermiogenesis and chromosomal aberrations. A clinical study of azoospermic and oligozoospermic men with normal and abnormal karyotype

Clinical examinations including cytogenetical analyses were performed in 356 male partners of barren couples, 176 with azoospermia and 180 men with sperm counts below 10 million/ml. The chromosomal aberrations observed were: Klinefelter's syndrome (15 cases), 46 XX (3), 47 XYY (1), Y-chromosome anomalies (5), robertsonian (8) and reciprocal autosomal translocations (1), and 46 XY 16 h + (1). If minor variants were excluded this gave an incidence of constitutional chromosomal abnormalities of 11.9% in the azoospermia group and 4.4% in the oligozoospermia group. The phenotypes expressed by the specific anomalies showed great variations and appeared to be practically indistinguishable from those individuals having a normal karyotype.     

Genetic localization of Cd63, a member of the transmembrane 4 superfamily, reveals two distinct loci in the mouse genome

We describe a patient with Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukaemia (ALL) who developed it 2.5 years after being diagnosed with myelodysplastic syndrome (MDS). The patient initially had refractory anaemia (RA), but progressed to refractory anaemia with excess blasts (RAEB) 2 years later, that terminated in ALL. An immunophenotypic analysis of the lymphoblasts revealed CD10 and CD19 positive cells. The karyotype was normal 46,XY in RA phase, 46,XY,20q-during the RAEB phase, and 46,XY,t(9;22)(q34;q11),20q-during the ALL phase. Furthermore, p190 BCR-ABL mRNA was detected in the ALL blasts. These findings indicate that this ALL arose from the MDS clone through multiple cytogenetic evolutions, the final event of which was the acquisition of p190 BCR-ABL type Ph1.     

Cytogenetic profile of lymphoma of follicle mantle lineage: correlation with clinicobiologic features

Conventional chromosome analysis (CCA) and interphase fluorescence in situ hybridization (FISH) was performed in 42 patients with mantle-cell lymphoma (MCL), with BCL1 rearrangement. The t(11;14)(q13;q32) or 11q abnormalities were detected by CCA in 34 cases, 20 of which had additional aberrations. A normal karyotype was observed in 8 cases. Probes detecting the chromosome aberrations that were observed in at least 3 cases by CCA, ie, +12, 13q14 deletion, and 17p deletion, were used for interphase FISH analysis. FISH detected total or partial +12, 13q14 deletion and 17p- in 28.5%, 52.4%, and 26% of the cases, respectively. The presence of these anomalies was not a function of karyotype complexity. Based on the results of CCA/FISH, three groups of increasing karyotype complexity were recognized: group 1, including 11 patients without detectable aberrations in addition to BCL1 rearrangement; group 2, including 14 patients with 1 to 2 additional anomalies; and group 3, including 17 patients with three or more additional anomalies. Clinical parameters associated with shorter survival were male sex (P =.006) and primary lymph-node involvement compared with primary bone marrow involvement (P =.015). Trisomy 12 was the only single cytogenetic parameter predictive of a poor prognosis (P =.006) and the best prognostic indicator was the derived measure of karyotype complexity (P <.0001), which maintained statistical significance in multivariate analysis (P<.0001). We arrived at the following conclusions: 13q14 deletion occurs at a high incidence in MCL; 17p deletion and total/partial +12 are relatively frequent events in MCL, the latter aberration being associated with a shorter survival; and the degree of karyotype complexity has a strong impact on prognosis in this neoplasia.     

i(18q) in amniotic and fetal cells with a normal karyotype in direct chorionic villus sampling: cytogenetics and pathology

A case of false-negative discrepancy between results of chorionic villi (direct preparation) and those of fetal tissue with an isochromosome 18q [i(18q)] in amniotic cells and fetal blood is reported. Fluorescence in situ hybridization (FISH) confirmed this uncommon chromosomal rearrangement. The fetus showed cyclopia and multiple congenital anomalies which have never been reported in cases of i(18q).