Deep Sequencing of Cell-Free Peripheral Blood DNA as a Reliable Method for Confirming the Diagnosis of Myelodysplastic Syndrome.

Background: Demonstrating the presence of myelodysplastic syndrome (MDS)-specific molecular abnormalities can aid in diagnosis and patient management. We explored the potential of using peripheral blood (PB) cell-free DNA (cf-DNA) and next-generation sequencing (NGS).

Materials And Methods: We performed NGS on a panel of 14 target genes using total nucleic acid extracted from the plasma of 16 patients, all of whom had confirmed diagnoses for early MDS with blasts <5%.

Supernumerary marker chromosomes detected in 100,000 prenatal diagnoses: molecular cytogenetic studies and clinical significance.

Objective: To evaluate the clinical significance of the supernumerary marker chromosomes (SMCs) detected during prenatal diagnosis.

Methods: We retrospectively studied cytogenetic/fluorescence in situ hybridization (FISH) results and clinical evaluation of 110 marker cases identified from approximately 100,000 cases referred for prenatal diagnosis. The clinical follow-up performed was focused on cases with de novo markers not derived from chromosome 15.

Trisomy recurrence: a reconsideration based on North American data.

Few reliable data exist concerning the recurrence risk for individual trisomies or the risk for recurrence of trisomy for a different chromosome. We collected records from two sources: (1) prenatal diagnoses performed at the Hopital Sainte-Justine in Montreal and (2) karyotype analyses performed at Genzyme. Using the standardized morbidity ratio (SMR), we compared the observed number of trisomies at prenatal diagnosis with the expected numbers, given maternal age-specific rates (by single year).

Partial duplication 2p as the sole abnormality in two cases with anencephaly.

Anencephaly/NTD has been observed in aneuploid and non-aneuploid individuals. We present two cases of anencephaly diagnosed prenatally with partial duplication of the short arm of chromosome 2 as the sole abnormality. The absence of aneuploidy involving other regions of the genome in these cases, further substantiates suggestions of the existence of a gene or genes on the short arm of chromosome 2 critical in the development of the central nervous system.

Residual risk for cytogenetic abnormalities after prenatal diagnosis by interphase fluorescence in situ hybridization (FISH).

Results from conventional cytogenetic studies on 21 609 amniotic fluid specimens were analyzed retrospectively to determine the residual risk for a cytogenetic abnormality if interphase FISH, capable of only detecting aneuploidy for chromosomes 13, 18, 21, X and Y, was performed and did not reveal an abnormality. Detection rates (the probability of detecting a cytogenetic abnormality when an abnormality is present) and residual risks (the likelihood of a cytogenetic abnormality, in view of normal interphase FISH results) were calculated for the four major clinical indications for prenatal diagnosis (advanced maternal age, abnormal maternal serum screen indicating increased risk for trisomy 18 or trisomy 21, abnormal maternal serum screen indicating increased risk for neural tube defects and ultrasound abnormality). Differences in detection rates were observed to depend on clinical indication and presence or absence of ultrasound abnormalities.

Prenatal diagnosis of 45,X and 45,X mosaicism: the need for thorough cytogenetic and clinical evaluations.

Objectives: Mosaicism involving a 45,X cell line is relatively common in prenatal diagnosis. In prenatally diagnosed cases, the prognosis of non-mosaic 45,X and 45,X/46,XY mosaicism are different. Therefore, accurate identification of a cell line containing Y chromosome is critical for genetic counseling and postnatal management.

A t(4;11)(q21;p15) in a case of T-cell lymphoma and a case of acute myelogenous leukemia.

The translocation (4;11)(q21;p15) has been observed in acute lymphoblastic as well as acute myeloid leukemias (ALL and AML, respectively). We report the first case of T-cell lymphoma with t(4;11)(q21;p15) and a case of AML. The clinical history of and cytogenetics in the latter is suggestive of a secondary leukemia; his karyotype revealed emergence of a t(3;11)(q21;q13) in addition to the t(4;11).