Does hand mirror morphology a useful diagnostic tool for the treatment decision of acute undifferentiated leukemia at admission?

Abstract: It is difficult how to manage acute undifferentiated leukemia in daily practice, but generally, hand mirror morphology provides ease to treat these patients. Thirty-nine years old male patient was admitted to with the complaints of echymosis, and pain at his left buttock due to an intramuscular injection for the treatment of previously diagnosed of the lower respiratory infection. Peripheral blood smear revealed >%50 blasts cells with a moderate nuclear: cytoplasmic ratio and one or more nucleoli. The blast cells showed a hand-mirror morphology and not harboring auer rods. According to the flow cytometric analysis the blastic cells do not represent to be originated from myeloid or lymphoid origin, because the cells harboring both of two cell lineages. AML-like therapy was commenced based on the positive myeloid markers including CD117 and CD135. Even though hand mirror morphology of the blasts usually demonstrates the lymphoid origin and the patients are treated as ALL like therapy, myeloid blasts rarely represents the same morphology, as was in our patient.

The clinical spectrum of a rare chromosomal abnormality: Isochromosome 18p.

Isochromosome 18p is a rare chromosomal disorder that occurs with a frequency of approximately one in every 180,000 live births, and affects both genders equally. MOst cases result from a de novo formation. In the literature, there are currently only a small number of reports that describe the phenotypic and clinical features of Isochromosome 18p. In this article, we report six cases that displayed the phenotypic and clinical features of Isochromosome 18p, and which were subsequently confirmed by conventional karyotyping and fluorescence in situ hybridization. We also discuss the clinical features of these patients in the context of the cases previously reported in the literature.

PRENATAL DIAGNOSIS OF DE NOVO SUPERNUMERARY MARKER CHROMOSOME ORIGINATED FROM CHROMOSOME 16 BY ARRAY-CGH.

A 33 years-old pregnant woman was referred for amniocentesis at 19 weeks of gestation due to abnormal serum biochemistry. A non-satellited, monocentric marker chromosome was observed with a frequency of 50% in cultured amniocytes. Parental karyotypes were normal. The marker chromosome was found to be derived from chromosome 16 by FISH and array-CGH analysis. Genetic counseling was given to parents and the family decided to terminate the pregnancy. Dysmorphic findings including; low set ears, exophtalmos depressed nasal bridge, large mouth and lips, posture anomalies at the extremities were detected at autopsy.

PRENATAL DIAGNOSIS OF DE NOVO PERICENTRIC INVERSION INV(2)(p11.2z13).

We here report a prenatal case with de novo pericentric inversion inv(2)(p11.2q13). A 20-years-old G1PO woman was referred for amniocentesis at 17 weeks of gestation, because of a positive second trimester screening test for aneuploidy. A de novo pericentric inversion inv(2)(p11.2q13) was detected during conventional cytogenetic analysis. Array-CGH analysis of the fetus showed no subtle chromosomal imbalances at the breakpoints. Genetic counseling was given to the family and the family decided to continue the pregnancy. To our knowledge, our case is the third prenatally detected de novo case with inv(2)(p11.2q13), and also the first case in which molecular karyotyping analysis were also applied.

22q11.2 syndrome due to maternal translocation t(18;22) (pl1.2;q11.2).

22q11.2 deletion syndrome is a pattern of malformations resulting from abnormalities during cephalic neural crest migration and during the development of the third and fourth branchial arch. It is also known as DiGeorge syndrome, as it is most often associated with a de novo 3 Mb hemizygous 22q11.2 deletion. The recognition of similarities and phenotypic overlap between DiGeorge syndrome and other disorders associated with genetic defects in 22q11 has led to an expanded description of the phenotypic features of this syndrome. Indeed, the extent of this phenotypic variability can often make it difficult to accurately diagnose DiGeorge syndrome. Tertiary monosomy resulting from the 3:1 segregation of the respective chromosomal segments of the chromosomes involved in a balanced translocation in meiosis is rarely reported in the literature. In this report, we present a female infant with dysmorphic facial features, microcephaly, a cleft palate, unilateral membranous choanal atresia, convulsions, hypocalcemia, semilobar holoporencephaly and echocardiographic abnormalities. To the best of our knowledge, this is the first description of a newborn displaying both DiGeorge syndrome and deletion 18p syndromes.

Prenatal diagnosis of a de novo supernumerary marker chromosome originating from chromosome 16.

Prenatal diagnosis of a de novo supernumerary marker chromosome originating from chromosome 16: A 37 year old pregnant woman was referred for amniocentesis at 18 weeks of gestation due to advanced maternal age and abnormal serum biochemistry. A nonsatellited, monocentric marker chromosome was observed with a frequency of 57% in cultured amniocytes. Parental karyotypes were normal. The marker chromosome was found to be derived from chromosome 16 by FISH using CEP16 and WCP16 probes. Marker chromosomes were not painted with M-FISH probe mixture, indicating an exclusively heterochromatin nature. CGH analysis using genomic DNA isolated from uncultured amniocytes also supported the M-FISH results. Genetic counseling was given to parents and the family decided to continue the pregnancy to term. The baby was born at 36 weeks of gestation without any dysmorphic features. Follow-up at 7 months of age revealed no developmental abnormalities.

Partial trisomy 4(q31qter) due to maternal 4;5 balanced translocation in a neonate.

We describe a male neonate with a duplication of 4(q31.3qter) due to unbalanced segregation of a maternal translocation (4;5)(31.3;p15.1). He has a high broad nasal bridge, large, low-set ears, epicanthal folds, long philtrum, retrognathia, high arched palate, wide-spaced nipples, bilateral single transverse palmar creases, bilateral clinodactyly of the fifth finger, right cryptorchidism, and ventricular and secundum type atrial septal defect.

Novel cytogenetic findings revealed by conventional cytogenetic and FISH analyses in leukaemia patients.

AIM: To describe novel cytogenetic findings in four leukaemia patients. METHODS: Conventional cytogenetic (CC) and fluorescence in situ hybridization (FISH) analyses were performed on bone marrow samples of four leukaemia patients. RESULTS: In this study, t(3;10)(q11;q25) and t(2;22)(p21;q11.2) were detected as novel translocations. t(8;16;21)(q22.1;q13;q22) and t(1;6;9;22)(p36.1;p21.3;q34;q11) were found as variant translocations, and these variant translocations were confirmed by Interphase-FISH and Multi-colour-FISH. CONCLUSION: Newly identified cytogenetic findings can lead us to characterize cytogenetic evolution of the haematological malignancies. Further investigations are certainly warranted to resolve the prognostic impact of these new cytogenetic abnormalities.

Subtelomeric chromosomal rearrangements detected in patients with idiopathic mental retardation and dysmorphic features.

Subtelomeric chromosomal rearrangements detected in patients with idiopathic mental retardation and dysmorphic features: Cryptic aberrations involving the subtelomeric regions of chromosomes are thought to be responsible for idiopathic mental retardation (MR) and multiple congenital anomalies, although the exact incidence of these aberrations is still unclear. With the advent of chromosome-specific telomeric Fluorescence In Situ Hybridization (FISH) probes, it is now possible to identify submicroscopic rearrangements of distal ends of the chromosomes that can not be detected by conventional cytogenetic methods. In this study, cryptic subtelomeric chromosomal aberrations were detected in two of ten patients with idiopathic MR and dysmorphic features by using FISH probes of subtelomeric regions of all chromosome arms. A cryptic unbalanced de novo translocation was detected between the subtelomeric regions of the chromosome 10p and 18p in a patient with severe mental retardation, sensorineuronal deafness and several dysmorphic features. In the other patient, with mild mental retardation and dysmorphic features, a de novo subtelomeric deletion of chromosome 2q was found. In conclusion, in both familial and sporadic cases with idiopathic MR and dysmorphic features, the detection of chromosomal aberrations including subtelomeric rearrangements is of great importance in offering genetic counseling and prenatal diagnosis.

Retinoic acid isomers protect hippocampal neurons from amyloid-beta induced neurodegeneration.

Attenuating amyloid-beta mediated neurodegeneration is of major therapeutic consideration in the potential treatment of Alzheimer disease. Previously, we found that a high dietary consumption of retinoic acid was associated with a reduced incidence of Alzheimer disease. Therefore, in this study, we investigated whether amyloid-beta mediated cell death in primary hippocampal neurons could be prevented by retinoic acid isomers. Our results suggest that retinoic acid isomers, including all-trans retinoic acid, 9-cis retinoic acid, and 13-cis retinoic acid, may play an important role in protecting neurons from amyloid-beta -induced cell death. Retinoic acid may therefore afford a novel therapeutic mechanism for the treatment and prevention of Alzheimer disease.

Parental origin and mechanisms of formation of cytogenetically recognisable de novo direct and inverted duplications.

Cytogenetic, FISH, and molecular results of 20 cases with de novo tandem duplications of 18 different autosomal chromosome segments are reported. There were 12 cases with direct duplications, three cases with inverted duplications, and five in whom determination of direction was not possible. In seven cases a rearrangement between non-sister chromatids (N-SCR) was found, whereas in the remaining 13 cases sister chromatids (SCR) were involved. Paternal and maternal origin (7:7) was found almost equally in cases with SCR (3:4) and N-SCR (4:3). In the cases with proven inversion, there was maternal and paternal origin in one case each. Twenty three out of 43 cytogenetically determined breakpoints correlated with common or rare fragile sites. In five cases, including all those with proven inverse orientation, all breakpoints corresponded to common or rare fragile sites. In at least two cases, one with an interstitial duplication (dup(19)(q11q13)) and one with a terminal duplication (dup(8) (p10p23)), concomitant deletions (del(8) (p23p23.3) and del(19)(q13q13)) were found.