Microarray-based comparative genomic hybridization (aCGH) between basic research and clinical diagnostic

In the vast spectrum of human pathology, a significant proportion is represented by genetic disorders. To elucidate the mechanisms leading to disease, various approaches have been used: G-banded karyotyping and FISH allow the survey of the entire genome for large aberrations or analysis of pre-defined segments, while sequencing detects nucleotide alterations with the prior requirement of knowing which DNA segment to address. The last two decades have seen the rise of another generation of investigative methods, such as aCGH, which inquire the condition of the whole genome at sequence level; starting as a research instrument, aCGH is increasingly regarded as a powerful diagnostic tool for clinical use. As an example of its utility in the diagnostic of mental retardation, we present three cases where aCGH contributed to the identification and refinement of the precise genetic aberrations

Genetic testing in myelodysplastic syndromes contribution in diagnosis, prognostic and clinical management

Myelodysplastic syndromes (MDS) represent a group of clonal hematological malignancies characterized by ineffective hematopoiesis. Other hematological disorders associating dysplastic features are grouped under the myelodysplastic/ myeloproliferative neoplasms (MDS/MPN) category. The great diversity of the acquired chromosomal abnormalities described in MDS highlights the molecular heterogeneity of these diseases. We report on 12 MDS and 3 MDS/MPN patients investigated by cytogenetic and molecular techniques (FISH). The most frequent chromosomal anomalies were 5q deletion and trisomy 8. Other trisomies, deletions and new translocations were also detected. MDS and MDS/MPN stand as challenging entities in hemato-oncology due to their heterogeneity. Thus, genetic testing provides important means for diagnosis confirmation and offers further insight into the prognosis and management of these patients

Rare hematologic neoplasms an acute megakaryocytic leukemia case report

Acute megakaryoblastic leukemia (AMKL) is a rare disorder in adults, particularly challenging due to difficulties in diagnosis, its complex genetic abnormalities and severe prognostic. A high percentage of AMKL cases bear cytogenetic abnormalities and, among them, 70-80% show complex karyotypes. We report on a 46 year-old male patient diagnosed with AMKL, after an initial evolution as acute lymphoblastic leukemia Burkitt-like. Highly complex chromosomal abnormalities were revealed by cytogenetic and molecular techniques (FISH), reflecting the underlying genetic instability. Our report emphasize the importance of both cellular and molecular approaches in onco-hematology, in order to accurately identify and refine genetic aberrations. As a consequence, better diagnosis and prognosis assessment is achieved, as well as understanding of pathogenic mechanisms

Pallister–Killian Syndrome versus Trisomy 12p—A Clinical Study of 5 New Cases and a Literature Review

Pallister–Killian syndrome (PKS) is a rare, sporadic disorder defined by a characteristic dysmorphic face, pigmentary skin anomalies, intellectual disability, hypotonia, and seizures caused by 12p tetrasomy due to an extra isochromosome 12p. We present three cases of PKS and two cases of trisomy 12p to illustrate and discuss features rarely cited in the literature, present certain particularities that not yet been cited, and analyze the differences between entities. Moreover, we present alternative methods of diagnosis that could be easily used in daily practice. Features not yet or rarely reported in PKS literature include marked excess of hair on the forehead and ears in the first months of life, a particular eye disorder (abnormal iris color with pointed pupil), connective tissue defects, repeated episodes of infection and autonomic dysfunction, endocrine malfunction as a possible cause of postnatal growth deficit, more complex sensory impairments, and mild early myoclonic jerks. After performing different combinations of tests, we conclude that MLPA (follow-up kit P230-B1) or array CGH using DNA extracted from a buccal swab is a reliable method of diagnosis in PKS and we recommend either one as a first intention diagnostic test. In cases without major defects associated (suspicion trisomy 12p), subtelomeric MLPA should be performed first