Sideroblastic anemia associated with thrombocytosis and a chromosome 3 abnormality

A unique patient with sideroblastic anemia and thrombocytosis with a recurrent and ultimately fatal thromboembolic phenomenon is described. Cytogenetic analysis of bone marrow metaphases revealed a pseudodiploid chromosome complement, 46,XY,ins(3;3)(q26;q21q26). The association of thrombocytosis and ins(3;3) in patients with preleukemia or myelogenous leukemia has been reported previously. The association of ins(3;3) and thrombocytosis in our patient with sideroblastic anemia suggests that the disorder may involve a hematopoietic progenitor cell capable of giving rise to all three cell lineages. Our findings also support the suggestion that a gene on the long arm of chromosome #3 may encode a protein that, at least in part, regulates megakaryopoiesis.     

Spontaneous clinical and cytogenetic remission of aplastic anemia in a patient with del(13q)

We describe the case of a 64-year-old Japanese man with pancytopenia. Bone marrow biopsy findings were consistent with aplastic anemia. The patient was treated by transfusions without immunosuppressive therapy. Chromosome analysis of bone marrow cells at 6 months after onset showed a 46,XY,del(13) (q14q22) karyotype. The pancytopenia resolved gradually over the next 5 years; chromosome analysis of bone marrow cells at that time yielded normal findings. To our knowledge, this is the first report of spontaneous hematologic and cytogenetic remission of aplastic anemia. These findings suggest that the abnormal clone with deletion of the long arm of chromosome 13 was not sufficient for clonal evolution in aplastic anemia in this case.     

Formation of double minutes by breakdown of a homogeneously staining region in a refractory anemia with excess blasts

A patient suffering from refractory anemia with excess blasts in transformation had four different bone marrow karyotypes. These were 46,XY; 45,X,-Y; 45,X,-Y, 5q-,19q+; and 43,X,-Y,-9,-17,5q-,+dmin. The most plausible explanation for this is proposed to be formation of a homogeneously staining region on chromosome #19, followed by its breakdown into double minutes.     

MLL-CBP fusion transcript in a therapy-related acute myeloid leukemia with the t(11;16)(q23;p13) which developed in an acute lymphoblastic leukemia patient with Fanconi anemia

We describe a boy with Fanconi anemia (FA) who developed acute lymphoblastic leukemia (ALL) (FAB-LI) followed by acute myeloid leukemia (AML) (FAB-M5) at relapse. The patient was diagnosed with early pre-B-cell ALL without preceding aplastic anemia and was treated with ALL-oriented chemotherapy which included doxorubicin (a total dose of 140 mg/m(2) administered), which is a topoisomerase II inhibitor. Complete remission was obtained, but after 38 weeks AML developed. The karyotype of ALL cells at diagnosis showed 46,XY, and that of AML cells at relapse was 46,XY, t(11;16)(q23;p13). An MLL gene rearrangement and MLL-CBP chimeric mRNA were found in AML, but not in ALL. A diagnosis of FA was confirmed by an increased number of chromosomal breaks and rearrangements in peripheral blood lymphocytes cultured with mitogen in the presence of mitomycin C. We conclude that this FA patient developed ALL followed by a therapy-related t(11;16)-AML resulting in an MLL-CBP fusion. Further examination of such patients would shed light on leukemogenesis in FA patients. Genes Chromosomes Cancer 27:264-269, 2000.     

Recurrent unbalanced whole-arm t(1;10)(q10;p10) in myelodysplastic syndrome: a case report and literature review

We report a patient with myelodysplastic syndrome (refractory anemia) showing the karyotype 46,XY,+1,der(1;10)(q10;p10), resulting in trisomy 1q and monosomy 10q abnormality. This finding suggests that either trisomy of 1q or centromeric connection between chromosomes 1 and 10, rather than the absence of 10q, might be essential toward neoplastic transformation.     

Biphenotypic leukemia with unusual chromosomal translocation in a patient treated for melanoma

A patient in complete remission from malignant melanoma but with refractory anemia after nitrosourea treatment developed acute biphenotypic leukemia. This disease, progression was accompanied by expansion of a cytogenetically abnormal clone. At first cytogenetic analysis, 1 year post discontinuation of chemotherapy, only 25% of the metaphases examined were hypodiploid with monosomy 7. Six months later, all of the metaphases seen were 45,XY,-7. Six months before overt acute leukemia was diagnosed, an additional chromosome abnormality emerged, t(2;3)(q31;q27). Although the translocation was present in all metaphases examined, the patient progressed into an acute leukemia with two components: one TdT-positive, Ia-positive, and the other TdT-negative, Ia-positive, monocytoid antigen-positive. This mixed leukemia was identified by double fluorescence staining for intranuclear TdT and surface labeling with a monocyte-specific monoclonal antibody.     

Systemic lupus erythematosus in a patient with refractory anemia

A 69-year-old man was diagnosed as having refractory anemia (RA), accompanied by pancytopenia of two years' duration, myelodysplasia in all three cell lines, abnormal karyotype of 46, XY, 20q--in bone marrow cells, and positive antinuclear and DNA antibody tests. One year after his first visit, he developed arthritis and maculopapular erythematous rashes. The histologic features of the skin lesions were similar to those of in discoid lupus erythematosus. He was diagnosed as having systemic lupus erythematosus supervening refractory anemia.     

A microdeletion syndrome due to a 3-Mb deletion on 19q13.2 – Diamond–Blackfan anemia associated with macrocephaly, hypotonia, and psychomotor retardation

We report on a boy with congenital pure red blood cell aplasia [Diamond Blackfan anemia (DBA)] and severe congenital hypotonia, macrocephaly, hypertelorism, a broad and tall forehead, medial epicanthus, and facial hypotonia with mouth-breathing and drooling, an affable and out-going personality, and a general psychomotor retardation. These features show similarity to the phenotype of the X-linked FG syndrome. DBA was diagnosed at the age of 4 months, and the boy underwent treatment with transfusion and with prednisolone. He had a normal 46, XY karyotype, but fluorescence in situ hybridization (FISH) analysis to metaphase chromosomes revealed a 3-Mb deletion on 19q13.2. This chromosomal region has previously been linked to the DBA phenotype and one 19q13 microdeletion has been identified in a patient with DBA. This deletion coincides with the deletion reported here. We suggest that the complex phenotype of our patient, including both DBA and the associated features, represent a microdeletion syndrome.     

Trisomy 13 as a primary chromosome aberration in acute leukemia.

Four patients with acute leukemia displayed trisomy 13 as the primary chromosome abnormality. The two patients with acute nonlymphocytic leukemia FAB-type M1 (ANLL-M1) had the karyotypes 47,XY,+13/48,XY,+13,+13 and 47,XX,+13, a patient with the hypogranular form of ANLL M3 had 47,XX,+13, and the fourth patient, who had acute undifferentiated leukemia (AUL), had the karyotype 47,XY,+13/48,XY,+8,+13. Including these four cases, a total of 24 hematologic neoplasms with an extra chromosome 13 as the sole aberration have now been reported. Except for the AUL, all have been of myeloid origin--20 ANLL, one myelodysplastic syndrome, and two chronic myeloproliferative disorders. Trisomy 13 as the sole acquired karyotypic abnormality therefore seems to be strongly associated with myeloid differentiation of the neoplastic cells and with a differentiation block leading to acute leukemia.     

Both alleles of the M235T polymorphism of the angiotensinogen gene can be a risk factor for myocardial infarction

We report two 46,XY female patients with two different de novo unbalanced translocations, each involving the chromosomal region 6p25. The patient with a 46,XY,der(6)t(X;6)(p21.2;p25) karyotype had a sex reversal phenotype. The patient with a 46,XY,der(13)t(6;13)(p25;q33) karyotype had a male pseudohermaphrodite phenotype. Multi-paint fluorescent in situ hybridization was performed to determine the origin of the derivative material on 6p and 13q. The association of abnormalities of the 6p25 region with either an Xp duplication or a 13q deletion is reported here for the first time.     

Sister chromatid exchange frequency in a retinoblastoma mosaic patient with del(13)

The frequencies of sister chromatid exchange (SCE) were investigated in different cell populations derived from a patient with retinoblastoma and 46,XY/46,XY,del(13) (q12.3q21.2) mosaicism. No differences in spontaneous or mitomycin C-induced SCE were detected between cell populations.     

Acquired inv(9): what is its significance?

Pericentric inversion of the heterochromatic region of chromosome 9 [inv(9)] is a common heteromorphism in the general population. It is presumed familial as there are no reports of de novo inv(9) chromosomes in constitutional karyotypes. We report 2 cases of acquired inv(9) chromosomes; 1 patient with acute myeloid leukemia, 46,XY,inv(9)(p11q13)[11]/46,XY[9], and a second with severe anemia, 46,XX,inv(9)(p11q13)[14]/46,XX[6]. The acquired nature of the inv(9) was confirmed by constitutional karyotyping and/or molecular analysis. The inv(9) in these patients may be a de novo inversion that cytogenetically mimics the constitutional inv(9) heteromorphism. Alternatively, it may be the result of neocentromere activation in 9q due to epigenetic events associated with the disease in these patients that results in a metacentric chromosome similarly mimicking the constitutional inv(9). One previous report of an acquired inv(9) was in a patient with essential thrombocythemia. The differences in clinical presentation may represent different underlying mechanisms generating the inv(9). The significance of an acquired inv(9) is unknown and will require reporting of additional cases.     

Two successful pregnancies in a 46,XY patient

Two successful pregnancies (singleton followed by twins) following ovum donation/in-vitro fertilization in a 46,XY woman have been studied. Although similar cases have previously been presented: in a pure XY patient and in a 45,X/46,XY patient, this case is one in which a subsequent successful pregnancy has resulted. In such patients, the rate of Caesarean section appears to be increased, and we postulate that the hypoplastic nature of the uterus, although able to respond quite well to both exogenous and endogenous hormones to accept and maintain a pregnancy, may lack the capability to respond fully in labour by dilating appropriately.      

46,XY女性性反转患者SRY基因的一个新突变类型

目的 研究46，XY女性性反转患者发病的分子机理。方法 应用聚合酶链反应(polymerase chain reaction，PCR)扩增1例性反转患者和其父亲的．SRY基因片段；PCR产物连接到pUCm-T载体上，在ABI 377-3自动测序仪上完成测序以查明突变；应用PCR-限制性酶切对DNA测序的结果进行检测。结果 发现该患者的SRY基因存在点突变(T387A)，导致SRY蛋白发生氨基酸翻译终止(酪氨酸129终止密码)，患者父亲的序列正常。由于患者SRY序列中增加一个Mae Ⅱ酶切位点，PCR-限制性内切酶酶切电泳检测，结果显示患者出现3条带(131bp、231bp和247bp)，而正常人出现2条带(131bp和478bp)，进一步验证了序列分析的结果。经查证数据库，该突变是一个未见报道的新型．SRY基因突变。结论 这一新型突变的发现，有助于进一步阐明46，XY女性性反转发病的分子机理。     

Cardiac surgery in a patient with idiopathic aplastic anemia: a case report

Major surgery in a patient with pancytopenia might be associated with increased surgical risks, especially for bleeding and infection. A 66-yr-old man was admitted to the hospital due to shortness of breath. His dyspnea was classified by the New York Heart Association (NYHA) as functional class III. Prior to admission, he had a 5-yr history of medical management for idiopathic aplastic anemia. The severity of aplastic anemia of the patient was graded as non-severe aplastic anemia. Echocardiography revealed reduced left ventricular function and severe aortic valve regurgitation (grade IV) with left ventricular end diastolic dimension measuring 87 mm. Because of dyspnea and echocardiographically documented aortic valve insufficiency, the patient underwent elective aortic valve replacement. Although extracorporeal circulation for valve operations might be associated with aggravation of impaired blood cell function, the patient recovered from surgery uneventfully. Here, we report a successful cardiac surgery with extracorporeal cardiopulmonary bypass in a patient with severe aortic valve insufficiency and concomitant idiopathic aplastic anemia.     

Trisomy 14 mosaicism in a liveborn male: clinical report and review of the literature

We present the history and results of chromosome analysis of a liveborn male with mosaic trisomy 14 who was initially evaluated for a congenital heart defect. His chromosome complement was 46,XY/47,XY,+14. The phenotype of the patient is similar in many respects to that of females previously reported with mosaic trisomy 14, whereas the patient's micropenis and cryptorchidism are consistent with findings in males with dup(14q).     

一例21号染色体三体嵌合型孤独症谱系障碍患儿的遗传学分析

目的对1例孤独症谱系障碍(autism spectrum disorder,ASD)伴有先天性心脏病的患儿进行细胞遗传学和分子遗传学分析,寻找其病因。方法取患儿及其父母的外周血进行常规染色体G显带核型分析,对患儿外周血提取的基因组DNA进行基于高通量测序的全外显子测序(whole exome sequencing,WES)和低覆盖度全基因组拷贝数变异测序(low-coverage massively parallel copy number variation sequencing,CNV-seq)检测分析,并利用染色体微阵列分析(chromosomal microarray analysis,CMA)进行验证。结果常规染色体G显带核型分析结果显示患儿及其父母染色体核型正常,患儿WES未检测到异常变异,而CNV-seq检测结果为47,XY,+21[10%]/46,XY[90%],提示存在低比例的21号染色体三体嵌合,CMA验证结果与CNV-seq结果一致。结论低比例的21号染色体三体嵌合除与唐氏综合征表型有关外,还可能与ASD的发生密切相关。基于高通量测序的WES及CNV-seq方法可为原因不明的ASD提供准确的遗传学诊断。     

Abnormal chromosome 9 in a neonate program. Report of three cases

We describe three cases with abnormal chromosome 9. Patient 1 shows translocation in a homologous chromosome, with a karyotype of 46,XX,t(9;9)(9pter----cen----9pter; 9qter----cen::9q13----9qter), 1qh+. This case has a variety of anomalies, including brain anomalies. Patient 2 shows a partial trisomy 9p with a karyotype of 47,XY,+del(9)(pter----q11:). The patient has the typical clinical features of 9p trisomy syndrome. Patient 3 is unique because of partial 9p tetrasomy mosaicism without phenotypic abnormalities; the karyotype is mos 46,XY/47,XY,+dic(9)(pter----cen----q21::q21----cen----pter).     

A cytogenetic survey of 449 patients in a Japanese institution for the mentally retarded

A cytogenetic survey was carried out on 449 patients (261 males and 188 females) in an institution for the mentally retarded in Japan. A total of 37 patients (8.1 %) were shown to have chromosome abnormalities. There were 33 individuals (7.3 %) with 21 trisomy. In addition, we found one patient with 46,XY/47,XY, + 12p, one with 46, XY, r(22), and one with 45, XY, -13, -14,+t(13q14q). Only one female was found to have an abnormal sex chromosome constitution, 47, XXX. The significant contribution of chromosome abnormalities in the etiology of mental retardation is also shown in the present survey. The most common chromosome abnormality was 21 trisomy, as seen in other similar surveys.     

Tetrasomy 13 as the sole cytogenetic abnormality in acute myeloid leukemia M1 without maturation

We report a case of acute myeloid leukemia (AML) M1 showing a 48,XY,+13,+13 karyotype. Treatment was according to the Medical Research Council AML14 trial protocol with two courses of DAT chemotherapy. Postchemotherapy bone marrow examination failed to show complete remission or cytogenetic normalization. Despite having resistant disease, the patient initially remained clinically well although requiring regular blood transfusions for anemia. However his leukocyte count gradually increased and he became symptomatic. He was treated subsequently with FLAG but died approximately 2 weeks later, 6 months after first presenting. Tetrasomy 13 as the sole cytogenetic abnormality has not been reported previously in M1 AML and has only been reported in three other AML cases, all with an immature phenotype and poor outcome.