De novo balanced reciprocal translocation 46,XY,t(6;8)(q13;q22).

A 5-month-old infant was examined because of minor multiple malformations. He was found to have a de novo blanced reciprocal translocation 46,XY,t(6;8(q13;q22). On follow-up at the age of 17 months his mental development was found to be within normal limits.     

North American Burkitt-type ALL with a variant translocation t(8;22)

A variant translocation, t(8;22) (q24;q12), was found in bone marrow (BM) and long-term cultured peripheral blood (PB) cells obtained from an American boy with Burkitt-type acute lymphoblastic leukemia (ALL-L3, French-American-British classification). Surface marker studies revealed a monoclonal immunoglobulin A (sIgA) with a lambda chain (74%) on the PB cells in a sample containing 74% blast cells. A table summarizing the cases with variant translocations in Burkitt diseases [Burkitt lymphoma (BL) and ALL-L3] is presented, and review of the published data indicates that, generally, the survival of patients with t(8;22)-type BL and ALL-L3 is short and comparable to that of patients with the more common translocation, t(8;14). There appears to be no relationship between t(2;8) or t(8;22) and a specific heavychain sIg. The karyotypes of the BM cells and those of the long-term cultured PB cells, though retaining t(8;22), differed from each other. Chromosomal analyses using cells from long-term culture may reveal karyotypic changes in addition to those seen on direct analysis. The key karyotypic anomaly in Burkitt-type diseases appears to be the breakage of chromosome #8 at band q24.     

Cytogenetic studies on African Burkitt's lymphoma cell lines: t(8;14), t(2;8) and t(8;22) translocations

Cytogenetic studies on ten African Epstein-Barr virus (EBV) positive Burkitt's lymphoma (BL) cell lines were performed. The usual translocation t(8;14) (q24;q32) was found in five of them, a deletion del(8) (q24→qter) in another one, while four variants were observed, two of these having a t(2;8) (p12;q24) translocation and two a t(8;22) (q24;q11) translocation. Other chromosome abnormalities were seen in seven of the cell lines, but these varied from one cell line to another. Thus, variant translocations, such as we describe here, are found in endemic BL cases. Two of these variants are identical to those previously identified in BL from nonendemic areas. The common chromosome abnormality of these BL cell lines was a rearrangement of the 8q24 band. The role of this constant cytogenetic change remains to be elucidated.     

Further characterization of acute myelogenous leukemia with t(8; 21) chromosome translocation

All seven patients with t(8; 21)(q22; q22) and one with a del(8)(q22) had a diagnosis of acute myelogenous leukemia (AML)-M2 type. Similar morphologies of leukemic cells with a t(8q?; 21q+) or with an 8q?, as well as the association of the latter with loss of a sex chromosome, indicated that the translocation or deletion of chromosome No. 8 at q22 may be essential to the phenotypic expression and loss of a sex chromosome in cells with the translocation. Seven patients (one in group I, four in group II, and two in group III) were in remission and four relapsed. All patients at relapse had acquired additional autosomal abnormalities, which were related to changes in cell morphology and relapse.     

Variant translocation in Burkitt's lymphoma: 8;22 translocation in a French patient with an Epstein-Barr virus-associated tumor

A variant translocation t(8;22)(q23;q11) has been found in tumor cells from a 19-year-old white man with an Epstein-Barr virus-associated Burkitt's lymphoma (BL). The tumor, which appeared 2 years after the patient had infectious mononucleosis, bore histopathological features characteristic of BL, although only the lymph nodes in the cervical region were involved. This case and some other recent cytogenetic observations of nonendemic BL emphasize the importance of chromosome #8 rearrangement in this B-cell-type lymphoma.     

A five-way complex translocation in a patient with chronic myelocytic leukemia: t(4;18;13;9;22)(q12;q11.2;q14;q34;q11.2)

A 10-year-old boy with chronic myelocytic leukemia was found to have a new complex Philadelphia translocation. All of the bone marrow cells and the peripheral blood cells had a rearrangement of a five-way translocation. t(4;18;13;9;22)(q12;q11.2;q14;q34;q11.2). The patient eventually died in blast crisis 6 years, 9 months later.     

Constitutional translocation t(4;22) (q12;q12.2) associated with neurofibromatosis type 2

We report on a female patient with bilateral acoustic neurinomas and other tumors in the central nervous system (neurofibromatosis type 2: NF2) and the constitutional translocation, t(4;22) (q12;q12.2). The precise identification of the translocation breakpoint (q12.2) on chromosome 22 implies the refined localization of a gene responsible for NF2, and would provide a clue to its molecular characterization and to the isolation of the gene. Chromosomes of a paraspinal neurinoma from the patient were also analyzed, and the same karyotype as seen in cultured peripheral lymphocytes was found. The patient's father was also a carrier of the translocation, but he had no clinical symptoms of NF2, nor did other relatives. Several explanations are offered for the different expression of the translocation between the patient and her father. © 1992 Wiley-Liss, Inc.     

Transmission of a balanced homologous t(22q;22q) translocation from mother to normal daughter

The transmission of a t(22q;22q) translocation is reported. The mother had had multiple miscarriages and carried both t(22q;22q) and t(22p;22p) portions of the rearrangement in a portion of her cells. The phenotypically normal daughter, who was the proband and was referred because of multiple miscarriages, also carried the t(22q;22q) translocation.     

Complex Ph1 translocation in chronic myeloid leukemia

This report describes a new case of chronic myeloid leukemia with an unusual Philadelphia chromosome translocation involving chromosomes No. 4,9, and 22; t(4,9,22) (q31;q34;q11).     

Constitutional translocation t(4;22) (q12;q12.2) associated with neurofibromatosis type 2.

We report on a female patient with bilateral acoustic neurinomas and other tumors in the central nervous system (neurofibromatosis type 2: NF2) and the constitutional translocation, t(4;22) (q12;q12.2). The precise identification of the translocation breakpoint (q12.2) on chromosome 22 implies the refined localization of a gene responsible for NF2, and would provide a clue to its molecular characterization and to the isolation of the gene. Chromosomes of a paraspinal neurinoma from the patient were also analyzed, and the same karyotype as seen in cultured peripheral lymphocytes was found. The patient's father was also a carrier of the translocation, but he had no clinical symptoms of NF2, nor did other relatives. Several explanations are offered for the different expression of the translocation between the patient and her father.     

Immunoblastic lymphoma following Hodgkin's disease: a case report with translocation t(8;14) in tumoral cells and sporadic t(7;14) in peripheral lymphocytes

A non-Hodgkin's lymphoma was observed in a patient who had been treated for Hodgkin's disease (HD). The initial treatment consisted of radiotherapy alone, but following three subsequent relapses, both chemotherapy and radiotherapy were administered several times. Twenty years later, the biopsy of an isolated cervical lymph node revealed a non-Hodgkin's lymphoma. The histologic subtype was immunoblastic. Cytogenetic studies of the tumoral cells revealed a t(8;14)(q24;q32) translocation. At the same time, multiple chromosomal rearrangements were observed in peripheral blood lymphocytes, especially t(7;14)(q35;q12), which was noted in 6 of 53 mitoses. This anomaly, frequently observed in patients with ataxia telangiectasia or severe immunodeficiency, has not previously been described in such circumstances.     

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.     

Occurrence of a variant Philadelphia translocation, t(10;22), in de novo acute megakaryoblastic leukemia

Acute megakaryoblastic leukemia (AMegL) in adults is a very rare subtype of acute myeloid leukemia (AML) and is characterized by a larger diversity of chromosomal abnormalities than the other subtypes, including 3q21q26 changes, aberrations of chromosomes 5 and 7, and the t(9;22)(q34;q11). We report the case of a 24-year-old patient with de novo AMegL and thrombocythemic cell count. Diagnosis was established with a bone marrow biopsy, and cytogenetics with G-banding revealed a t(10;22), which by FISH, was found to be a variant Philadelphia translocation involving chromosome 10q in all 20 metaphases analyzed. We believe that this is the first report of de novo AMegL with this chromosomal abnormality, and its possible correlation with morphology and thrombocytosis is discussed.     

A novel sequence-based approach to localize translocation breakpoints identifies the molecular basis of a t(4;22)

Low copy repeats (LCRs) located in 22q11.2, especially LCR-B, are susceptible to rearrangements associated with several relatively common constitutional disorders. These include DiGeorge syndrome, Velocardiofacial syndrome, Cat-eye syndrome and recurrent translocations of 22q11 including the constitutional t(11;22) and t(17;22). The presence of palindromic AT-rich repeats (PATRRs) within LCR-B of 22q11.2, as well as within the 11q23 and 17q11 regions, has suggested a palindrome-mediated, stem-loop mechanism for the generation of such recurring constitutional 22q11.2 translocations. The mechanism responsible for non-recurrent 22q11.2 rearrangements is presently unknown due to the extensive effort required for breakpoint cloning. Thus, we have developed a novel fluorescence in-situ hybridization and primed in-situ hybridization (PRINS) approach and rapidly localized the breakpoint of a non-recurrent 22q11.2 translocation, a t(4;22). Multiple primer pairs were designed from the sequence of a 200 kb, chromosome 4, breakpoint-spanning BAC to generate PRINS probes. Amplification of adjacent primer pairs, labeled in two colors, allowed us to narrow the 4q35.1 breakpoint to a 6.7 kb clonable region. Application of our improved PRINS protocol facilitated fine-mapping the translocation breakpoints within 4q35.1 and 22q11.2, and permitted rapid cloning and analysis of translocation junction fragments. To confirm the PRINS localization results, PCR mapping of t(4;22) somatic cell hybrid DNA was employed. Analysis of the breakpoints demonstrates the presence of a 554 bp palindromic sequence at the chromosome 4 breakpoint and a 22q11.2 location within the same PATRR as the recurrent t(11;22) and t(17;22). The sequence of this breakpoint further suggests that a stem-loop secondary structure mechanism is responsible for the formation of other, non-recurrent translocations involving LCR-B of 22q11.2.     

PLP1 duplication at the breakpoint regions of an apparently balanced t(X;22) translocation causes Pelizaeus–Merzbacher disease in a girl

Fonseca ACS, Bonaldi A, Costa SS, Freitas MR, Kok F, Vianna‐Morgante AM. PLP1 duplication at the breakpoint regions of an apparently balanced t(X;22) translocation causes Pelizaeus–Merzbacher disease in a girl. PLP1 (proteolipid protein1 gene) mutations cause Pelizaeus–Merzbacher disease (PMD), characterized by hypomyelination of the central nervous system, and affecting almost exclusively males. We report on a girl with classical PMD who carries an apparently balanced translocation t(X;22)(q22;q13). By applying array‐based comparative genomic hybridization (a‐CGH), we detected duplications at 22q13 and Xq22, encompassing 487–546 kb and 543–611 kb, respectively. The additional copies were mapped by fluorescent in situ hybridization to the breakpoint regions, on the derivative X chromosome (22q13 duplicated segment) and on the derivative 22 chromosome (Xq22 duplicated segment). One of the 14 duplicated X‐chromosome genes was PLP1.The normal X chromosome was the inactive one in the majority of peripheral blood leukocytes, a pattern of inactivation that makes cells functionally balanced for the translocated segments. However, a copy of the PLP1 gene on the derivative chromosome 22, in addition to those on the X and der(X) chromosomes, resulted in two active copies of the gene, irrespective of the X‐inactivation pattern, thus causing PMD. This t(X;22) is the first constitutional human apparently balanced translocation with duplications from both involved chromosomes detected at the breakpoint regions.     

一例母源性46,Y,der(X)t(X;Y)(p22;q11)染色体非平衡易位患儿的遗传学分析

目的对1例临床表征为身材矮小、鼻根部内陷、双侧隐睾、智力低下患儿进行遗传学分析,探讨该染色体结构异常与临床表征之间的关系。方法应用G显带染色体核型分析及染色体微阵列分析(chromosomal microarray analysis,CMA)技术对患儿进行遗传学检测,并对其父母进行外周血染色体核型分析。结果G显带分析结果显示患儿染色体核型为46,Y,der(X)t(X;Y)(p22;q11),mat。CMA检测结果提示患儿X染色体短臂Xp22.33p22.31存在约8.3 Mb片段缺失,Y染色体长臂Yq11.221qter存在约43.3 Mb片段重复。其父亲染色体核型正常,母亲染色体核型结果为46,X,der(X)t(X;Y)(p22;q11)。结论患儿携带母源性der(X)t(X;Y)(p22;q11)染色体非平衡易位,携带者的表型与其性别以及X染色体缺失片段的大小和位置密切相关。男性携带者智力障碍、生长发育落后等异常表型较女性更为严重。     

Inherited translocation t(4;5) discovered on prenatal diagnosis

We report an apparently balanced reciprocal t(4q;5q) translocation ascertained coincidentally on amniocentesis in a phenotypically normal male fetus and found to be inherited in his mother and maternal grandmother. No banding study was available at the time of the amniocentesis, and the chromosomal status of his parents was unknown. Because of the possibility that this finding might be a de novo, unbalanced translocation, the pregnancy was terminated. Subsequently, the translocation was found to be apparently balanced, but so unequal that both unbalanced translocation products are presumed to be lethal. Thus, it is predicted that only carriers and normal individuals will be conceived and viable in this family. We are unaware of previously published observations on a similar (4q;5q) translocation.     

t( 12;21): A new recurrent translocation in acute lymphoblastic leukemia

A t(12;21)(p11 -p12;q22) was detected by chromosome painting in three patients with acute lymphoblastic leukemia (ALL) among eight ALL cases with 12p- abnormalities. The three leukemias had similar immunophenotypes (DR+, CD10 +, CD19 + ). Fluorescence in situ hybridization (FISH) experiments using YAC clones from 21q21-q22 were performed to better localize the breakpoint on chromosome 21. This breakpoint was localized to 21q22.2 in one patient. Although only one case of ALL with t( 12;21) has been reported previously, the present results suggest that t( 12;21) is a recurrent translocation in ALL. Genes Chrom Cancer 9:186-191 (1994). © 1994 Wiley-Liss, Inc.