Cytogenetic findings in familial B-cell chronic lymphocytic leukemia: a report of two cases in a family

Familial B-cell chronic lymphocytic (B-CLL) leukemia has been defined as an entity epidemiologically different from sporadic B-CLL. Cytogenetic abnormalities in familial B-CLL, studied either by conventional cytogenetics or by interphase fluorescence in situ hybridization (i-FISH), have rarely been reported. We report a two-case family affected with B-CLL showing two different abnormal karyotypes detected by conventional cytogenetics [46,XX,del(7)(q32) and 46,XY,add(1)(p36),del(6)(q21)] but sharing a del(13)(q14) at the D13S319 locus, detected by interphase fluorescence in situ hybridization.     

Karyotypic findings in two cases of male breast cancer

Male breast cancer is uncommon; so far, only 10 cases with chromosome banding analysis have been published. We report the cytogenetic findings of two invasive breast cancers in two Caucasian men lacking a history of familial breast cancer and more than 70 years of age. Both had ductal carcinomas with lymphangiosis carcinomatosa and positive lymph nodes at diagnosis. Strong expression of estrogen receptor, weak expression of progesterone receptor, and lack of expression of androgen receptor by both tumors were demonstrated by immunohistochemistry, as well as lack of expression of p53 and C-ERB-B-2. The karyotypes were 45 approximately 46,XY,-Y[4],-7[2],+8[2],t(8;12)(q21;q24)[3], del(9)(q22)[3],del(11)(p11p14)[5],del(18)(q21)[7], t(19;20)(p10;q10)[8] [cp13] and 61 approximately 69,XXXY,-Y[3], del(2)(p21)[4],del(3)(p22q26)[3],-4,-4[5],+5,+5[5], dic(5;11)(p14;q23)[3],del(6)(q23)[4],del(8)(p21)[3],-9[4],-11[4],+ i(12)(p10)[4],-16[3],del(17)([13)[5],del(18)(q21)[4],+19[5], +20[4][cp7], respectively. Although the available data on male breast cancer are still very limited, our findings confirm that gain of an X chromosome, loss of the Y chromosome, gain of chromosome 5, and loss of material from chromosomes 17 and 18 are nonrandom aberrations in male breast cancer. Trisomy 8, characteristic of ductal carcinomas, was found in one case.     

Karyotypic evolution in acute myelomonocytic leukemia with pericentric inversion of chromosome 16

A 37-year-old Japanese male patient with acute myelomonocytic leukemia subtype M4 (according to FAB classification) associated with bone marrow eosinophilia and specific chromosome abnormalities: a pericentric inversion of chromosome 16, inv(16)(p13q22); a long arm deletion of chromosome #7, del(7)(q22q34); and a gain of chromosomes #8 and #22 is reported. In addition to the modal karyotype, 47,XY,7q-,inv(16),+22, there were three other clones whose karyotypes were 46,XY,inv(16); 47,XY,inv(16),+22; and 48,XY,+8,inv(16),+22. As these karyotypes were related to each other, the presence of multiple clones indicated that karyotypic evolution had occurred. The karyotypic evolution associated with 7q- has not been reported previously in patients with M4Eo with inv(16).     

Tricho-rhino-phalangeal syndrome type I with severe mental retardation due to interstitial deletion of 8q23.3–24.13

Here we report on a 13-year-old boy who had an interstitial deletion of the long arm of chromosome 8 [46,XY,del(8)(pter→q23.3::q24.13→qter)]. He had the facial features of the tricho-rhino-phalangeal (TRP) syndrome and severe mental retardation, but lacked multiple exostoses. This is the first report with such a peculiar combination of abnormalities and interstitial deletion of 8q.     

Tricho-rhino-phalangeal syndrome type I with severe mental retardation due to interstitial deletion of 8q23.3-24.13

Here we report on a 13-year-old boy who had an interstitial deletion of the long arm of chromosome 8 [46,XY,del(8)(pter----q23.3::q24.13----qter)]. He had the facial features of the tricho-rhino-phalangeal (TRP) syndrome and severe mental retardation, but lacked multiple exostoses. This is the first report with such a peculiar combination of abnormalities and interstitial deletion of 8q.     

Cytogenetic subtype involving chromosome 13 in lipoma. Report of three cases

We report three lipomas with rearrangements of chromosome 13. The karyotype of the tumors studied were 45,XX,-8,+der(8)t(8;13)(q22;q12),del(10)(p12),-13; 46,XY,del(13)(q12q22), and 46,XY,t(11;12)(q23;q13),del(13)(q12q22), respectively, revealing common involvement of band 13q12 in the rearrangement. Three other lipomas with aberrations of bands 13q12-q13 have been reported, suggesting that such tumors with abnormalities of chromosome 13 could represent a subgroup of lipoma in addition to those already reported with abnormalities of chromosomes 12q and 6p. The rearrangements of #13 in all these cases also involved loss of the band 13q14 to which the antioncogene associated with retinoblastoma and osteosarcoma is localized. Detailed clinical, histopathologic, and molecular studies should help to further characterize the various cytogenetically defined subgroups of lipoma.     

Chromosomal anomaly of 6q in chronic myelogenous leukemia (CML)

Anomalies of chromosome 6q, along with other chromosomal anomalies, are described in the bone marrow cells of two patients with chronic myelogenous leukemia (CML). One patient, a 14-year-old male, developed the karyotype 46,XY,t(1;6)(p36;q15),del(3)(q25),del(17)(p11),? inv(17)(q12q24) during blastic crisis of his disease. The other patient, a 24-year-old male, had the karyotype 46,XY,del(6)(q13),t(9;22)(q34;q11) during the early phase of his disease and evolution of i(17q) in the karyotype late in the disease.     

5p;12q translocation with manifestations of cri du chat syndrome and Marfanoid arachnodactyly

A 12-year-old boy with a history of a mewing cry after birth, severe mental retardation, Marfanoid arachnodactyly, general osteomalacia and multiple bone fractures was found to have a de novo 5p;12q chromosomal translocation. The karyotype is 46,XY,t(5;12)(12qter----12q24.1::5p15----cen----5qt er; 12pter----cen----12q24.1). The karyotypes of other examined family members are normal. The manifestations of cri du chat syndrome are explained by the loss of a small segment of 5p15 which is responsible for the major stigmata of the syndrome, and the abnormalities of the osseous system may be the results of untreated vitamin D resistant rickets.     

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. © 2002 Wiley‐Liss, Inc.     

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.     

Translocation (8;13)(q24.2;q33) in a malignant rhabdoid tumor of the liver

A case of malignant rhabdoid tumor of the liver associated with hypercalcemia of malignancy was studied. The karyotype of the liver primary was 46,XY,t(8;13)(q24.2;q33)[7]/46,XY[13], and of the brain metastasis 46,XY,t(8;13)(q24;q33)[5]/46,XY,t(7;13)(p14;q22) [3]/46,XY,t(1;2;3)(q25;q21;p21) [2]/46,XY[13], respectively. Band 8q24 was previously reported to be rearranged in two malignant rhabdoid tumors, one renal and one hepatic.     

A case of human chimerism detected by unbalanced chromosomal translocation

Chimerism in humans is usually found only because of discrepancies in unique blood group typing or sex chromosome complements. We describe a case found because of an inherited chromosomal translocation. A female carrier of the balanced reciprocal translocation t(14;20)(q31;q13.3) had a twin pregnancy. After birth the B-twin, a girl, was found to have the balanced translocation. The A-twin, a severely malformed and stillborn boy, had two different karyotypes; a normal 46,XY and an unbalanced translocation derivative 46,XY,-14, +der(14)t(14;20)(q31;q13.3). He was a dispermic chimera, formed by two fertilized oocytes.     

染色体46,XX,t(1;4)(q42;q35)平衡易位一例

目的报道染色体平衡易位家系1例。方法检查父母及女儿染色体,采用外周血淋巴细胞培养法,G显带。结果父亲染色体核型为46,XY。母亲染色体核型为46,XX,t(1;4)(q42;q35)。女儿染色体核型为46,XX,der(1)t(1;4)(q42;q35),der(4)t(1;4)(q42;q35)。结论母亲染色体发生t(1;4)(q42;q35)平衡易位并遗传给下一代。     

Familial reciprocal translocation, t(2;10)(p24;q26), resulting in duplication 2p and deletion 10q

We describe a familial reciprocal translocation between the distal part of the short arm of chromosome 2 and the long arm of chromosome 10. Five individuals in two generations had multiple congenital anomalies. Their karyotypes were 46, XX or XY,−10, + der(10), t(2;10)(p24;q26). Seven persons were balanced translocation carriers whose karyotypes were 46, XX or XY, t(2;10)(p24;q26). Common manifestations included mental retardation, strabismus, narrow high-arched palate, wide alveolar ridges, other facial abnormalities, genital abnormalities and mutism. The phenotype of the unbalanced individuals is compared to that of previously published cases of the syndrome of partial duplication 2p and to reported patients with partial deletion of 10q.     

Identification of de novo chromosome rearrangements: five cases analyzed with differential chromosome painting

We report on five cases of de novo structural chromosome rearrangements that were difficult to identify by conventional G-banding analysis. In all five cases, differential chromosome painting (DCP) provided evidence for the presence of an additional segment and its origin. A combination of DCP with subsequent conventional fluorescence in situ hybridization (FISH) analysis using adequate locus-specific probes and reexamination of G-banding patterns resulted in successful identification of the rearrangements. Their karyotypes were finally interpreted as 46,XY,der(1)(qter --> q42.1::p36.3 --> qter) in case 1; 46,XY,der(8)(8pter -->8q24.3::8q24.3 --> 8q23.2::?p11.2 --> ?ps) in case 2; 47,XY,+der(10)(pter --> q11) in case 3; 46,XX,der(3)(17pter --> 17p11.2::3p26 --> 3qter) in case 4; and 46,XY,dup(1) (pter --> q32::q25 --> qter) in case 5.     

Interstitial del(20)(q11.2q12) - clinical and molecular cytogenetic characterization

A 2-year-old male patient with dysmorphic facial features and multiple congenital anomalies suggestive of a chromosome syndrome is presented. The facial features consisted of a large and high forehead, mild metopic ridging, a small triangular face, depressed nasal bridge, microphthalmia (right more than the left), protruding ears, and mildly prominent anteverted nose with long and smooth philtrum. Cytogenetic analysis showed 46,XY,del(20)(q11.2q12). Parental karyotypes were normal. Molecular characterization of del(20)(q11.2q12) by high-resolution microarray comparative genomic hybridization (arrayCGH) showed an approximately 6.8 Mb deletion. To our knowledge this is the first report of a de novo interstitial del(20)(q11.2q12) characterized by arrayCGH.     

Heterogeneity of PLAG1 gene rearrangements in pleomorphic adenoma

Pleomorphic adenoma (PA), a benign mixed salivary gland tumor, has been associated with abnormal karyotypes in up to 70% of cases, with nonrandom involvement of 8q12, the locus of the pleomorphic adenoma (PLAG1) gene. In this study, cytogenetics and fluorescence in situ hybridization (FISH) were used to investigate PLAG1 involvement in PA from seven patients. There were two males and five females ranging in age from 25 to 65 years. Samples of parotid gland tissue from the tumor sites, set up as solid tumor cultures, showed a normal karyotype in two cases [46,XY;46,XX] and cytogenetic abnormalities in five cases (71%). The abnormalities comprised one variant translocation [t(1;4;8)(p32;q35;q12)], two classic translocations [t(5;8)(p13;q12)], one novel deletion [del(12)(p11.2p12.1)], and a novel insertion [ins(9;8)(p22;q12q21.1)]. FISH was performed in all cases by using two probes from the RP11 library, flanking PLAG1; a sequence 1.48 megabases (Mb) upstream and another 2.27 Mb downstream, covering a total area of 3.8 Mb. The PLAG1 gene was intact and normally situated in four cases - the 46,XY, 46,XX, del(12p), and one t(5;8). PLAG1 was disrupted in three cases - one t(5;8), ins(9;8), and t(1;4;8). In addition, genomic instability was seen in two cases, one with PLAG1 amplification in the form of a homogeneously staining region, and the other in der(8) ring formation. The data provide further unique cases showing the complexity of PLAG1 gene rearrangements in PA.     

Chromosome abnormalities and rare fragile sites detected in azoospermia patients

Summary We have examined constitutional chromosome abnormalities and fragile sites in 40 patients with azoospermia. Chromosome abnormalities were found in four cases. Three cases showed a deletion of the long arm of the Y chromosome 46,X,del(Yq) and the other case had a ring of G group chromosome 46,XY,r(G). In a rare fragile sites test, four fragile site carriers were detected and three rare autosomal fragile sites were identified; fra(8)(q24.1), fra(11)(p15.1), and fra(17)(p12). The expression of these fragile sites were induced specifically by AT-specific DNA ligands, such as distamycin A and Hoechst 33258. In addition, one patient was found to be the case of double ascertainment of fragile sites, fra(8)(q24.1) and fra(17)(p12). The overall frequency of distamycin A-inducible fragile sites in azoospermia patients appeared to be higher than those reported for Japanese healthy subjects and cancer patients. However, no significant relation among fragile sites, clinical and histological findings has been detected so far.     

三例世界首报染色体异常核型分析

目的对3例世界首报染色体异常核型进行研究探讨.方法采用外周血淋巴细胞72h培养,制备染色体.3例标本用G、C-显带法进行染色体核型分析.结果有两例染色体发生平衡易位.1例Y染色体臂内倒位.发现3种人类染色体异常核型,分别为46,XY,t(1;10)(q25;q24);46,XX,t(1;12)(q42;p13);45,X/46,X,inv(Y)(q11q12).经鉴定确定为世界首报核型.结论染色体异常是导致自然流产及性腺发育不全的重要原因.     

Two cases with interstitial deletions of chromosome 2 and sex reversal in one.

We present two children with de novo interstitial deletions of the long arm of chromosome 2 (karyotypes 46,XY, del(2)(q31.1q31.3) and 46,XY, del(2)(q24.3q31.3), respectively). The first child had severe learning difficulties, growth retardation, unilateral ptosis, small palpebral fissures, a cleft uvula, and bilateral cutaneous syndactyly of the second and third toes. Despite her male karyotype, she had female external genitalia with hypoplasia of the clitoris and labia minora. This is the first reported case of feminization of the external genitalia in a genotypic male with an interstitial deletion of chromosome 2q31 and adds to the growing amount of evidence for a gene involved in sex determination in this chromosome region. The second child had severe mental and growth retardation, ptosis, down-slanting palpebral fissures, low-set ears, micrognathia, finger camptodactyly, and brachysyndactyly of the second to fifth toes. The clinical manifestations associated with deletions of 2q31 to 2q33 are similar to those found with proximal deletions at 2q24 to 2q31 and of band 2q24, suggesting that the phenotype may result from haploinsufficiency for one or more genes located at 2q31. Microsatellite marker studies showed that both children had paternally derived deletions that included the HOXD gene cluster and the EVX2, DLX1, and DLX2 genes known to be important in limb development.