A 14q+ chromosome in adult T-cell leukemia

Chromosome studies were conducted on two patients with adult T-cell leukemia. In both patients, a marker chromosome 14q+ and a structural change involving chromosome 1 with trisomy of the q arm were found in peripheral blood leukocytes. The 14q+ marker chromosome had resulted from translocation from #5p in one patient and #5q in the other patient. The present and previous studies suggest that the donor chromosomes involved in the 14q+ translocation are variable. This indicates that the 14q+ marker chromosome rather than the donor chromosome is intimately related with adult T-cell leukemia.     

Marker chromosome 1q+ in acute lymphocytic leukemia

This paper presents the results of a cytogenetic analysis on a patient with acute lymphocytic leukemia (ALL) type L2 according to the FAB classification. Of the metaphases examined, 69.3% belong to the aberrant clone of pseudodiploid karyotype. Marker chromosome 14q+ has been identified in all the cells of the clone. Duplication was found in 30% of the metaphases, and in 15% triplication of the proximal segment of the long arm of chromosome #1 (q11-q21). In one metaphase the long arm of chromosome #1 is made up of segment q11-q21 four times repeated. Aberrations of chromosome #1 support the idea that heterochromatic region may be related to the higher degree of the cell malignity.     

Osteoid osteomas with chromosome alterations involving 22q

Cytogenetic analysis was performed in two osteoid osteomas. In both, the modal chromosome number was 46. One of the cases presented a del(22)(q13.1) as the sole clonal chromosome alteration. The other had clonal monosomies of chromosomes 3, 6, 9, 17, 19, and 21, as well as a +del(22)(q13.1) was detected as a non-clonal chromosome alteration. There is only one osteoid osteoma reported so far showing clonal karyotypic alterations. The cytogenetic behavior of osteoid osteomas described here was different from that of the osteoid osteoma of the literature. Numerical alterations of chromosomes 3, 6, 9, 17, 19, 21 and 22 have been described in several neoplasias including bone tumors. The breakpoint of chromosome 22 involves a region where important genes for the regulation of the cell cycle have been mapped.     

A translocation breakpoint at chromosome band 12q13 associated with B-cell chronic lymphocytic leukemia.

Low-grade B-cell lymphoproliferative disorders are frequently associated with an extra copy of chromosome 12. This well-documented acquired anomaly is one of the most specific numerical chromosome alterations to occur in human hematological malignancies. We have cytogenetically characterized bone marrow and peripheral blood cells from a patient with B-cell chronic lymphocytic leukemia (CLL) having a unique acquired translocation involving chromosomes 6 and 12, t(6;12) (p21.3;q13), which implicates band 12q13 as the site of the gene(s) important in this lymphoproliferative B-cell disorder. Aneuploidy, in the form of trisomy of chromosome 12, is not a requirement for neoplastic transformation in B-cell CLL, but gene rearrangement (present case) or nondisjunctional acquisition of additional copies of defective genes on chromosome 12 at band q13 may be involved in the genesis or progression of this disorder.     

Expression of bcl-3 in chronic lymphocytic leukemia correlates with trisomy 12 and abnormalities of chromosome 19

The bcl-3 gene at chromosome 19q13 encodes a member of the IkB family involved in regulating the nuclear factor kB pathway. Originally identified by its involvement in the t(14:19)(q32;q13), bcl-3 expression recently has been reported in 12% of non-Hodgkin lymphomas and 41% of Hodgkin lymphomas. Because the t(14;19) is detected most commonly in chronic lymphocytic leukemia (CLL), we assessed for bcl-3 expression using immunohistochemical analysis in 72 CLL cases with immunophenotypic and cytogenetic data. Of 72 CLL cases, 12 (17%) were bcl-3+. Expression of bcl-3 correlated with an atypical immunophenotype, defined using the World Health Organization scoring system. Expression also correlated with trisomy 12 and chromosome 19 abnormalities but was not limited to cases with the t(14:19)(q32;q13). Although the mechanism of bcl-3 expression is unclear, these results raise the possibility that bcl-3 may be involved in the pathogenesis of this subset of tumors and could be a potential target for investigational therapies.     

Muellerian aplasia associated with ring chromosome 8p12q12 mosaicism

We report on a woman with Muellerian aplasia, renal and skeletal anomalies, and minor dysmorphic signs. Conventional cytogenetic analysis revealed mosaicism for a small supernumerary, undefinable ring chromosome. Chromosome microdissection and reverse painting demonstrated that this marker contained pericentric material from chromosome 8 (8p12q12). Thus, we identified a Muellerian aplasia phenotype with partial trisomy 8 mosaicism.     

A der(19)t(12;19)(q12;p13.3) in a case of pediatric acute leukemia with unusual immunophenotype

We describe a case of acute leukemia in a child with an unusual immunophenotype and a novel cytogenetic abnormality. The leukemia blasts expressed myeloid, natural killer and B-lineage associated antigens. Cytogenetics showed the presence of a novel unbalanced chromosomal translocation, der(19)t(12;19)(q12;p13.3). The patient achieved and maintained remission with myeloid-directed chemotherapy. The differential diagnosis of the immunophenotype and the potential fusion genes are discussed.     

Boy with a chromosome del (3)(q12q23) and blepharophimosis syndrome.

We report on a 6-year-old boy with de novo 46,XY,del(3)(q12q23) and bilateral blepharophimosis, ptosis, epicanthus inversus, in addition to multiple other anomalies. Since 4 previously reported cases of interstitial deletion of 3q involving 3q23 band are clinically similar, we propose this blepharophimosis sequence due to 3q23 deletion as a further "contiguous gene syndrome."     

Trisomy/ tetrasomy of chromosome 8 and +i(8q) as the sole chromosome abnormality in three adult patients with myelomonocytic leukemia

We report three cases of tetrasomy 8 associated with myeloid disease. Two patients had chronic myelomonocytic leukemia (CMMoL) and the other had acute monocytic leukemia (AML M5 FAB). Two patients had trisomy/tetrasomy chromosome 8 as the sole abnormality. The other patient with CMMoL had two normal 8 chromosomes plus one isochromosome 8q; this is the first case of long arm chromosome 8 tetrasomy without short arm 8 monosomy. This cytogenetic finding suggests the importance of the genes located in the long arms of chromosome 8.     

Partial trisomy 12q: a clinically recognisable syndrome. Genetic risks associated with translocations of chromosome 12q.

A newborn child with an unusual facial appearance and multiple abnormalities was found to be trisomic for a large part of 12q as a result of adjacent 1 segregation of a familial translocation, t(9;12) (p24;q21.2). A combination of cytogenetic analysis, clinical features, and enzyme marker studies allows an accurate assessment of the breakpoints. Although trisomic for a considerably larger area of 12q than other reported cases, there are many similar features suggesting that trisomy 12q is a clinically recognisable syndrome. The frequency and mode of segregation of 12q translocations and their implications for genetic counselling are discussed.     

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12

Deletions in chromosome 17q12 encompassing the HNF1β gene cause cystic renal disease and maturity onset diabetes of the young, and have been recently described as the first recurrent genomic deletion leading to diabetes. Earlier reports of patients with this microdeletion syndrome have suggested an absence of cognitive impairment, differentiating it from most other contiguous gene deletion syndromes. The reciprocal duplication of 17q12 is rare and has been hypothesized to be associated with an increased risk of epilepsy and mental retardation. We conducted a detailed clinical and molecular characterization of four patients with a deletion and five patients with a reciprocal duplication of this region. Our patients with deletion of 17q12 presented with cognitive impairment, cystic renal disease, seizures, and structural abnormalities of the brain. Patients with reciprocal duplications manifest with cognitive impairment and behavioral abnormalities, but not with seizures. Our findings expand the phenotypic spectrum associated with rearrangements of 17q12 and show that cognitive impairment is a part of the phenotype of individuals with deletions of 17q12.     

Reassessment of a chromosome 12q + marker by fluorescent in situ hybridization (FISH)

We present a case previously described by Jenkins et al. (1983) as atypical Down syndrome (DS). The initial diagnosis was first made on the basis of phenotypic and cytogenetic data. This analysis was supported by studies of superoxide dismutase (SOD1) activity that maps to band 21q22.1. Results from phenotypic, chromosome banding and SODI studies suggested a karyotype of 46,XX,—12, + t(12pter to 12qter::21q21 to 21q22.?2). Using fluorescent in situ hybridization (FISH) for chromosome painting with DNA libraries derived from sorted human chromosomes to stain selectively the chromosomes No. 21 and No. 12, we demonstrate that the marker chromosome 12q+ has no chromosome 21 content but it is derived from chromosome 12.     

Autopsy findings of ectodermal dysplasia and sex development disorder in a fetus with 19q12q13 microdeletion

A 5,6 Mb de novo 19q12-q13.12 interstitial deletion was diagnosed prenatally by array-comparative genomic hybridization in a 26 weeks male fetus presenting with intra-uterine growth retardation, left clubfoot, atypical genitalia and dysmorphic features. Autopsic examination following termination of pregnancy identified a severe disorder of sex development (DSD) including hypospadias, micropenis, bifid scrotum and right cryptorchidism associated with signs of ectodermal dysplasia: scalp hypopigmentation, thick and frizzy hair, absence of eyelashes, poorly developed nails and a thin skin with prominent superficial veins. Other findings were abnormal lung lobation and facial dysmorphism.This new case of DSD with a 19q12q13 deletion expands the phenotypic spectrum associated with this chromosomal rearrangment and suggests that WTIP is a strong candidate gene involved in male sex differentiation.     

Blastic transformation associated with 5q- and 12p-

A case of acute myeloblastic leukemia secondary to polycythemia vera suggests that the t(3;21) translocation is not restricted to blastic phases of chronic myelocytic leukemia (CML) but can be associated with blastic phases occurring after other myeloproliferative syndromes. All published cases were in myeloid crises. Furthermore, this translocation may have been induced by mutagenic effects of either 32P or various chemotherapies administered in this case. In the nine cases reported (including ours), hydroxyurea and busulfan were most frequently used (each drug was used separately in six cases and in association in three cases). Even if the t(3;21) translocation is partly therapy induced, this chromosomal abnormality appears to characterize myeloid crises of myeloproliferative syndromes (often CML, seldom polycythemia vera).     

Two cousins with partial trisomy 12q and monosomy 12p recombinants of a familial pericentric inversion of the chromosome 12

Partial trisomy 12q and monosomy 12p lead to multiple malformation syndromes. Instead of trisomy 12q that has been reported as a clinically identifiable syndrome, monosomy 12p is characterized by a wide phenotypic spectrum. We report two cousins suffering from severe mental retardation, seizures, and dysmorphic features related to a trisomy 12q24.3-->qter and a monosomy 12p13-->pter resulting from a familial pericentric inversion of chromosome 12. In an attempt to improve the clinical delineation of these two syndromes, we compared our two patients with previous reports of these aneusomies. This review emphasizes the high frequency of familial translocations, including a breakpoint at 12q24 involved in trisomy 12q whereas monosomy 12p occurs most frequently de novo. Despite the poor specificity of the signs, this comparison allowed us to determine the clinical features present in more than 20% of patients with trisomy 12q or monosomy 12p. We particularly emphasize some consistent leading features of monosomy 12p, including microcephaly, dental, cardio-vascular, extremity, and sensorial abnormalities, initially not reported as recurrent in this syndrome.