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Objective The objective was to determine the risk of sampling error in amniocentesis and chorionic villus sampling (CVS) in singleton and multiple pregnancies. Data from this and other published studies were used to discuss current practice guidelines for molecular identity testing. Method Clinical and laboratory records of all patients undergoing molecular-based identity testing in our clinical laboratory from July 2002 until March 2008 were reviewed. DNA microsatellite testing was performed to determine zygosity in multiple pregnancies and maternal cell contamination (MCC) in both singleton and multiple pregnancies. Results MCC was detected in 6/148 (4%) CVS and 1/87 (1%) amniotic fluids from singleton pregnancies. In two of the CVS, only maternal cells were found. In 2/24 (8%) twin pregnancies, the same fetus was tested twice. In a total of 285 pregnancies (235 singleton, 24 twin, 26 with ≥ 3 fetuses), without molecular identity testing, four women would have received erroneous results. Conclusion Current guidelines recommend molecular identity testing for MCC in conjunction with molecular diagnostic testing, but not for cytogenetic testing. No published guidelines were found for zygosity testing in multiple pregnancies. We suggest that identity testing be considered for all prenatal testing of multiple pregnancies, especially if CVS is performed. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Multiple studies have reported a significant treatment-free remission (TFR) rate of 50%-60% in patients with chronic myeloid leukaemia (CML) who discontinue tyrosine kinase inhibitor (TKI) therapy. However, the remaining half of these patients still require re-initiation of TKI therapy for leukaemia control. It remains unclear if TKI drugs should be switched for re-therapy in patients who failed the first TFR (TFR1) attempt. Our study attempted to determine whether dasatinib therapy after TFR1 failure post-imatinib discontinuation could improve the likelihood of TFR2. Of 59 patients who lost molecular response after imatinib discontinuation for TFR1, 55 patients (93.2%) were treated with dasatinib, of whom 49 (89.1%) regained MR4.5 or deeper response, with a median time of 1.85 months to achieve MR4.5. Dasatinib was discontinued in 35 patients for TFR2 attempt, of whom 26 patients (74.28%) lost MMR and 6 (17.14%) MR4. Risk factor analysis for the TFR2 after dasatinib discontinuation suggested three significant factors: (1) doubling time of BCR::ABL1 transcript following TFR1 attempt, (2) rapid regaining of molecular response following dasatinib therapy and (3) undetectable BCR::ABL1 transcript prior to TFR2 attempt. The present study showed that dasatinib does not increase the TFR2 rate in general, but a selected group of patients could benefit from this approach., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

The doubling time (DT) of the BCR-ABL1 quantitative polymerase chain reaction (qPCR) transcript level reflects the re-growing fraction of leukaemic cells after discontinuation of tyrosine kinase inhibitor (TKI). The present study analyzed monthly DT within six months after imatinib discontinuation in 131 patients. Monthly DT was calculated as x = ln(2)/K, where x is the DT and K is the fold BCR-ABL1 change from the previous value divided by the number of days between each measurement. The optimal DT value was determined as 12·75 days at two months using a recursive partitioning method. The patients were stratified into three groups: the high-risk group (DT<12·75 days but >0, with rapidly proliferating chronic myeloid leukaemia (CML) cells; n = 26) showed the lowest molecular relapse-free survival (mRFS) of 7·7% at 12 months, compared to 53·6% in the intermediate-risk group (DT≥12·75 days, with slowly proliferating CML cells; n = 16) or 90·0% in the low-risk group (DT≤0, i.e., without proliferating CML cells; n = 71; P < 0·001). Monthly assessment of DT helps identify high-risk patients for treatment-free remission failure with an imminent risk of molecular recurrence, and to define low-risk patients who can be spared the frequent monitoring of monthly molecular tests., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Although total duration of tyrosine kinase inhibitor (TKI) therapy and of molecular response at 4 log reduction or deeper (MR4) correlates with treatment-free remission (TFR) success after TKI discontinuation, the optimal cut-off values of the duration remain unresolved. Thus, 131 patients were enrolled into the Canadian TKI discontinuation study. The molecular relapse-free survival (mRFS) was defined from imatinib discontinuation till molecular recurrence, that is, major molecular response (MMR) loss and/or MR4 loss. We evaluated mRFS at 12 months after imatinib discontinuation, analyzed it according to the imatinib treatment duration and MR4 duration, and calculated P value, positive (PPV) and negative predictive value (NPV) in the yearly cut-off period of time. The shortest cut-off was sought that met the joint criteria of a P value ≤ 0·05, PPV ≥ 60% and NPV ≥ 60%. We propose six years as the shortest imatinib duration cut-off with a P value 0·01, PPV 68% and NPV 62%: The patients treated with imatinib duration ≥ 6 years showed a superior mRFS rate (61·8%) compared to those with less treatment (36·0%). Also, 4·5 years MR4 duration as the shortest cut-off with a P value 0·003, PPV 63% and NPV 61%: those with MR4 duration ≥ 4·5 years showed a higher mRFS rate (64·2%) than those with a shorter MR4 duration (41·9%)., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Jacobsen syndrome (JS) is a disorder of developmental delay, growth retardation, thrombocytopenia, dysmorphic features, and cardiac abnormalities, among other congenital anomalies. JS is caused by contiguous gene deletion in distal chromosome 11q, generally varying in size from 7 to 20 Mb. Periventricular nodular heterotopia (PVNH) is a neuronal migration disorder in which neurons are abnormally located in nodules along the edges of the lateral ventricles. PVNH can also be seen with other congenital anomalies, including a recurrent association with distal limb defects. Transverse limb defects have previously been reported in two patients with JS. We report on a patient with a 3.162 Mb interstitial deletion at chromosome region 11q24 overlapping the region commonly affected in JS. The patient had PVNH and a transverse limb reduction defect, with minimal typical findings of JS. This is the first report of PVNH associated with a microdeletion at chromosome 11q and may represent an expansion of the phenotypic spectrum associated with JS. This is the third report of transverse limb reduction defects in association with JS, supporting a widening of the skeletal phenotypic spectrum in JS to include more severe limb anomalies. ETS1 is proposed as a candidate gene for involvement in limb anomalies in JS., (© 2013 Wiley Periodicals, Inc.)

Distal 5q-trisomy has been reported in less than 30 patients, with craniosynostosis present in five. We report two new patients with distal 5q-trisomy craniosynostosis. Patient 1 had mild Kleeblattschädel with synostosis of multiple sutures together with wide and medially deviated thumbs and halluces, indicative of Pfeiffer syndrome. Cytogenetic and CGH analyses showed a karyotype of 46,XY,der(10)t(5;10)(q33;q26.3). Patient 2 had a prominent forehead and ridging of the metopic suture. Craniosynostosis of the metopic suture was shown by CT scan. Cytogenetic and CGH analyses disclosed a karyotype of 46,XX,der(17)t(5;17)(q35.1;p13.3). Of the 22 previously reported patients, all had microcephaly and 14 had an abnormal skull shape. Our results support the previous finding that distal 5q-trisomy together with an extra copy of the MSX2 gene leads to abnormal closure of sutures and craniosynostosis., ((c) 2007 Wiley-Liss, Inc.)

We report on trisomy of the short arm of the X chromosome (Xp11.2 --> pter) due to a de novo unbalanced X;13 translocation diagnosed prenatally in a female fetus. Amniocentesis was performed at 20-weeks' gestation following ultrasound finding of a Dandy-Walker malformation. The trisomy of Xp11.2 --> pter was confirmed with fluorescence in situ hybridization (FISH), using an X chromosome painting probe and telomeric FISH probes specific for the short arm of chromosome X. The karyotype was defined as 46,XX,der(13)t(X;13)(p11.2;p11.2). Molecular analysis suggested that the extra Xp material was of paternal origin. FISH analysis with an XIST probe showed that the derivative chromosome 13 did not include the XIST locus at the X-inactivation center (XIC). A complex phenotype was seen at birth including macrosomia, facial dysmorphism with preauricular tag, congenital heart defects, and structural brain malformations. Because the derivative chromosome was not subject to X inactivation, functional disomy of Xp11.2 --> pter most likely accounts for the abnormal phenotype in this patient., (2005 Wiley-Liss, Inc.)