PubMed Health⌕ Search

Biomedical subjects

Anita Heller

Publications and source records attributed to Anita Heller.

At least 19 recordsLinked to original sources
PubMed2005

Dup(13)(q14.2-q14.3): yet another new differential diagnostic aspect for short stature-like phenotype.

We report on the case of a pregnant woman with hyposomia who was previously suspected of having Turner syndrome. Prenatal cytogenetic diagnostics showed a fetal karyotype of 46,XX,dup(13)(q14.2q21.1) ish.13q14(RB1 x 3). Parental and grandparental chromosome analyses were performed and the dup(13) was found to be of maternal origin (de novo). The pregnancy was continued and a healthy female child was born with normal development apart from growth retardation. The reported chromosomal aberration is, together with two other cases reported in the literature, the first hint of a short stature-like phenotype due to dup(13)(q14.2q14.3).

Adult↗
PubMed2005

Detection of cryptic chromosomal aberrations in the in vitro non-proliferating cells of acute myeloid leukemia.

A total of 22 acute myeloid leukemia (AML) cases were analyzed by cell-specific comparative genomic hybridization (micro-CGH). Conventional banding analysis identified a monosomy 7 in six (group I), a trisomy 8 in eight (group II) and a normal karyotype in eight cases (group III). A total of 32 additional chromosomal imbalances was detected and confirmed in two independent micro-CGH experiments. However, only in 9 of the 22 cases (group I: 4 cases; group II: 1 case; group III: 4 cases) the existence of 11 of the 32 (34.5%) detected copy number alterations could be confirmed by other fluorescence in situ hybridization (FISH) approaches. These results lead to two conclusions: i) in the in vitro non-proliferating population of AML tumor cells one can detect cryptic chromosomal aberrations, which might constitute tumor markers of diagnostic and prognostic value; ii) The results of CGH need to be checked by other approaches.

Acute Disease↗
PubMed2005

New rearrangement t(3;17)(q26.3;q12) in an AML patient with a poor outcome.

In more than 90% of acute promyelocytic leukemia (APL) cases a reciprocal translocation t(15;17)(q22;q12) can be observed. The RARalpha gene on 17q12 is known to have other translocation partners than PML (in 15q22) in a minority of APL cases. Here, we describe a previously unrecorded chromosomal translocation involving the RARalpha gene and an unknown partner on chromosome 3. The chromosomal rearrangement was studied in detail by 24-color-FISH using whole chromosome painting probes plus multicolor banding. Thus, the breakpoint could be characterized as t(3;17) (q26;q12). In this case 10% of blasts showed AML-M3 characteristics although typical rearrangements with RARalpha were not detected by molecular methods. The characterization of the present and other comparable APL-cases with exceptional translocation partners of PML or RARalpha will help to enlighten the understanding of the pathogenesis of APL.

Adult↗
PubMed2005

Three new cases with a supernumerary ring chromosome 1.

We report on three cases with a cytogenetically identical ring chromosome containing euchromatin from the long arm of chromosome 1 (r[1][::p11.1-->q21.1::]). Two cases were newborn males (Cases 1 and 2) and the third one was prenatally identified as female (Case 3). Mosaicism was present in all three cases in different degrees, i.e. 48%, 25% and 14% of the cells, respectively. Clinical signs and symptoms vary between the three cases. The results of our three cases are compared with those from the literature.

Chromosome Banding↗
PubMed2004

Genotype/phenotype analysis in a patient with pure and complete trisomy 12p.

Reports on patients with pure and complete trisomy 12p are rare. Up to now, 12 cases have been described in the literature. Here, we report on the genotype/phenotype-correlation of a female patient with a pure trisomy 12p. Conventional cytogenetic studies on peripheral blood chromosomes as well as molecular cytogenetic (fluorescence in situ hybridization, FISH) techniques including whole chromosome painting (WCP), comparative genomic hybridization (CGH), multicolor-banding (MCB) detected a female karyotype with an abberant chromosome 12:46,XX,der(12).ish dup(12)(pter --> q24.3::p11.2 --> pter). In addition to the trisomy 12p specific clinical hallmarks, the patient showed some features of Pallister-Killian syndrome (PKS) such as sparse hair, macroglossia, and epilepsy. These findings contribute to the genotype/phenotype correlation in trisomy 12p patients.

Abnormalities, Multiple↗
PubMed2004

Characterization of a highly aberrant plasma cell leukemia karyotype: a case report.

We report on a 72-year-old patient with a clinically diagnosed plasmocytoma which developed to a plasma cell leukemia (PCL) with so far unrecorded complex translocations. As GTG-banding was not able to resolve all karyotypic changes, multiplex-fluorescence in situ hybridization (M-FISH) in combination with microdissection based comparative genomic hybridization (micro-CGH) and multicolor banding (MCB) have been done. Using these molecular cytogenetic approaches the karyotype of the PCL case can be described as: 51,XY,-1,-1,+3,+der(5)t(5;11;1)(5pter right curved arrow 5q13-q14::11q24 right curved arrow 11q25::1q12 right curved arrow 1qter),+7 or +der(7)t(7;1)(7qter right curved arrow 7p15::1p31.1 right curved arrow 1pter),+8,+der(9)t(1;9)(1qter right curved arrow 1q12::9q12 right curved arrow 9pter),der(11)t(1;11;1)(1pter right curved arrow 1p31.1::11p15.5 right curved arrow 11q25::1q12 right curved arrow 1qter),-13,der(14)t(X;14)(Xqter right curved arrow Xq21.3::14pter right curved arrow 14qter),+15,+18,der(19)t(9;19)(9qter right curved arrow 9q12::19q11 right curved arrow 19pter),+i(19)(q10). The case shows one of the most complex karyotypic rearrangements ever described in PCL and indicates two additional chromosomal regions which may contain genes of interest for the development of this hematological disorder: loss of 1p10-p31.1 material and gain of Xq21.3-qter.

Aged↗
PubMed2004

Breakpoint differentiation in chromosomal aberrations of hematological malignancies: Identification of 33 previously unrecorded breakpoints.

Routine cytogenetic analysis provides important information of diagnostic and prognostic relevance for hematological malignancies. In spite of this, poorly spread metaphase chromosomes and highly rearranged karyotypes with numerous marker chromosomes, are often difficult to interpret. In order to improve the definition of chromosomal breakpoints multicolor banding (MCB) was applied on 45 bone marrow samples from patients suffering from hematological malignancies like myelodysplastic syndrome (MDS), acute myelocytic leukemia (AML), chronic myelocytic leukemia (CML) or acute lymphoblastic leukemia (ALL). The breakpoints defined by GTG banding were confirmed by MCB in 8 cases, while in the remaining 37 cases the breakpoints had to be redefined. In 20/45 cases the breakpoints could only be characterized after application of MCB. In summary, 73 different breakpoints were characterized, thereof 33 were previously undescribed. Eleven cases showed known acquired aberrations and 21 cases had previously described aberration types such as del(5q-), del(7q-), del(13q-) or t(1;5) as sole rearrangement or in connection with other complex ones. In a total of 11 cases 19 breakpoints as described before were involved in hematological malignancies, while in 14 cases 33 breakpoints were identified which have not been described previously. Thus, MCB has proven to be a powerful and reliable method for screening of chromosomal aberrations, which considerably increased the accuracy of cytogenetic diagnosis.

Adult↗
PubMed2003

Small supernumerary marker chromosomes (SMCs): genotype-phenotype correlation and classification.

Small supernumerary marker chromosomes (SMCs) are present in about 0.05% of the human population. In approximately 30% of SMC carriers (excluding the approximately 60% SMC derived from one of the acrocentric chromosomes), an abnormal phenotype is observed. The clinical outcome of an SMC is difficult to predict as they can have different phenotypic consequences because of (1). differences in euchromatic DNA-content, (2). different degrees of mosaicism, and/or (3). uniparental disomy (UPD) of the chromosomes homologous to the SMC. Here, we present 35 SMCs, which are derived from all human chromosomes, apart from chromosome 6, as demonstrated by the appropriate molecular cytogenetic approaches, such as centromere-specific multicolor fluoresence in situ hybridization (cenM-FISH), multicolor banding (MCB), and subcentromere-specific multicolor FISH (subcenM-FISH). In nine cases without an aberrant phenotype, neither partial proximal trisomies nor UPD could be detected. Abnormal clinical findings, such as psychomotoric retardation and/or craniofacial dysmorphisms, were associated with seven of the cases in which subcentromeric single-copy probes were proven to be present in three copies. Conversely, in eight cases with a normal phenotype, proximal euchromatic material was detected as partial trisomy. UPD was studied in 12 cases and subsequently detected in two of the cases with SMC (partial UPD 4p and maternal UPD 22 in a der(22)-syndrome patient), indicating that SMC carriers have an enhanced risk for UPD. At present, small proximal trisomies of 1p, 1q, 2p, 6p, 6q, 7q, 9p, and 12q seem to lead to clinical manifestations, whereas partial proximal trisomies of 2q, 3p, 3q, 5q, 7p, 8p, 17p, and 18p may not be associated with significant clinical symptoms. With respect to clinical outcome, a classification of SMCs is proposed that considers molecular genetic and molecular cytogenetic characteristics as demonstrated by presently available methods.

Amniotic Fluid↗
PubMed2003

A multiple translocation event in a patient with hexadactyly, facial dysmorphism, mental retardation and behaviour disorder characterised comprehensively by molecular cytogenetics. Case report and review of the literature.

UNLABELLED: We report a 13-year-old female patient with multiple congenital abnormalities (microcephaly, facial dysmorphism, anteverted dysplastic ears and postaxial hexadactyly), mental retardation, and adipose-gigantism. Ultrasonography revealed no signs of a heart defect or renal abnormalities. She showed no speech development and suffered from a behavioural disorder. CNS abnormalities were excluded by cerebral MRI. Initial cytogenetic studies by Giemsa banding revealed an aberrant karyotype involving three chromosomes, t(2;4;11). By high resolution banding and multicolour fluoresence in-situ hybridisation (M-FISH, MCB), chromosome 1 was also found to be involved in the complex chromosomal aberrations, confirming the karyotype 46,XX,t(2;11;4).ish t(1;4;2;11)(q43;q21.1;p12-p13.1;p14.1). To the best of our knowledge no patient has been previously described with such a complex translocation involving 4 chromosomes. This case demonstrates that conventional chromosome banding techniques such as Giemsa banding are not always sufficient to characterise complex chromosomal abnormalities. Only by the additional utilisation of molecular cytogenetic techniques could the complexity of the present chromosomal rearrangements and the origin of the involved chromosomal material be detected. Further molecular genetic studies will be performed to clarify the chromosomal breakpoints potentially responsible for the observed clinical symptoms. CONCLUSION: This report demonstrates that multicolour-fluorescence in-situ hybridisation studies should be performed in patients with congenital abnormalities and suspected aberrant karyotypes in addition to conventional Giemsa banding.

Abnormalities, Multiple↗
PubMed2003

First patient with trisomy 21 accompanied by an additional der(4)(:p11 --> q11:) plus partial uniparental disomy 4p15-16.

We report on a rare additional numerical chromosomal aberration in a child with Down syndrome due to free trisomy 21. The karyotype showed 48,XY,+21,+mar after GTG banding, with the marker present in 80% of cells. The supernumerary marker chromosome (SMC) was as small as approximately one-third of 18p, and with the recently developed centromere-specific multi-color fluorescence in situ hybridization (cenM-FISH) technique, it was shown that the SMC was a derivative chromosome 4. The SMC was not specifically stained by arm-specific probes for chromosome 4; thus, it has been described as der(4)(:p11 --> q11:). Microsatellite analysis resulted in a partial maternal uniparental isodisomy (UPD) for chromosome 4p15-16 and a maternal origin for two chromosomes 21. Until now only two similar cases have been described in the literature, but without clarifying the origin of the SMC and without looking for an additional UPD. This is the only reported case of a UPD 4p in a liveborn child.

Chromosome Aberrations↗
PubMed2003

Karyotyping of human synaptonemal complexes by cenM-FISH.

The purpose of this work was to adapt the recently described centromere-specific multicolour (cenM-) FISH technique to human meiotic cells, and evaluate the usefulness of this multiplex fluorescence method for karyotyping human synaptonemal complex (SC), previously analysed by immunocytogenetic approaches. The results obtained demonstrate that cenM-FISH is a reliable one-single-step method, which allows for the identification of all SC present in pachytene spreads. Moreover, when cenM-FISH is applied after immunocytogenetic analysis, the number and distribution of MLH1 foci per chromosome can be established and recombination analysis for each chromosome can be performed easily.

Centromere↗
PubMed2003

Highly complex karyotypic changes in acute myelogenous leukemia: a case report.

We report on a patient with a clinically diagnosed acute myelogenous leukemia (AML) with so far unrecorded complex translocations. As GTG-banding was not able to resolve all karyotypic changes, spectral karyotyping (SKY) and multiplex-fluorescence in situ hybridization (M-FISH) were performed for comparison. Both methods gave nearly identical results, however, they were unable to characterize all involved chromosomal breakpoints in detail. Thus, multicolor banding (MCB) technique was applied and its results were confirmed for two large derivative chromosomes by microdissection and reverse painting. Using this battery of molecular cytogenetic approaches the karyotype of this AML case could be described as 40 approximately 44,XY,der(1)t(1;5;8;20) (1qter-->1p12::5q14.3-->5q15 or 5q15-->5q14.3::8p11.2-->8p23.? 3::20p11.1-->20p13),del(2)(q12),der(3)t(3;6),der(5)t(5;18) (5p15.33-->5q11::18q21.3-->18q23),del(6),-8,der(9)t(9;17;15),der(10)t(3;10),del(11)(q24),-15,-16,del(17),der(18) t(8;18;5;2;20)(8q24.3-->8q24.2 or 8q24.2-->8q24.3::18p11.22-->18q21.3::5q14.3-->5q11::2q32-->2q12::20q13.2-->20q13.33), der(20)t(1;20;18)(1p36.33-->1p31.3-22.3::20p11.1-->20q11.2 or 20q11.2-->20p11.1::18p11.22-->18p11.32).

Chromosome Banding↗
PubMed2003

Detailed Hylobates lar karyotype defined by 25-color FISH and multicolor banding.

A comprehensive and detailed comparative chromosome map of the white-handed gibbon (Hylobates lar = HLA) has been established by hybridizing the recently developed complete human multicolor banding (MCB) probe set on metaphase chromosomes of a male HLA lymphoblastoid cell line. Thus, it was possible to precisely determine the breakpoints and distribution plus orientation of specific DNA-regions in this cytogenetically highly rearranged species compared to Homo sapiens (HSA). In general, the obtained results are in concordance with previous molecular-cytogenetic studies. In this study all 71 breakpoints present in HLA compared to HSA could be determined exactly. This study is a valuable complement to our knowledge on the phylogeny of huminoid chromosomes.

Animals↗