Saethre­Chotzen syndrome with an atypical phenotype: identification of TWIST microdeletion by array CGH.

Saethre­Chotzen syndrome is a very rare autosomal dominant congenital disorder characterized by craniosynostosis and acrocephalosyndactyly. It is caused by a mutation in TWIST1, located on chromosome 7p21. A shortage of functional TWIST1 protein affects the development and maturation of cells in the skull, face, and limbs. The patient described in this report displayed craniofacial features classic for Saethre­Chotzen syndrome, including craniosynostosis, low-set ears, small pinna with prominent crura, a high-arched palate, and a simian crease on the left hand. He did not have the limb anomalies commonly seen in patients with Saethre­Chotzen syndrome, and the results of conventional chromosome analysis were normal. However, results of a microarray-based comparative genomic hybridization (array CGH) study confirmed the karyotype of46,XY.7p21.1p15.3(15,957,375-20,331,837)x1, a region that includes TWIST1. Subsequent fluorescent in situ hybridization analysis confirmed this result. No other chromosome was involved in the rearrangement. This case illustrates the important contribution of array CGH to the identification of TWIST microdeletions, even in a patient not showing the phenotype typical of Saethre­Chotzen syndrome.

Acupuncture attenuates neuronal cell death in middle cerebral artery occlusion model of focal ischemia.

OBJECTIVES: This study was designed to investigate the neuroprotective effect of acupuncture in the middle cerebral artery occlusion-induced ischemia model. METHODS: Sprague-Dawley rats were randomly divided into two experimental groups: middle cerebral artery occlusion group (MCAO, n=8), and middle cerebral artery occlusion plus acupuncture group (MCAO + Acu, n=8). Acupuncture stimulation was given immediately after reperfusion. The effect of its stimulation to both GB34 and GB39 on the size of the brain infarct and the functional status of the brain cells after middle cerebral artery occlusion was examined by nissl staining and neuron-specific nuclear protein immunohistochemistry. RESULTS: The infarction volume was significantly decreased in the MCAO + Acu group (16.4 +/- 4.8%), compared with the MCAO group (39.9 +/- 10.2%). The number of neuron-specific nuclear protein-positive cells in the MCAO group was significantly decreased by 42.3 +/- 12.6% in the striatum and by 45.8 +/- 5.8% in the motor cortex, but the neuron-specific nuclear protein-positive cells in the MCAO + Acu group were rescued by 67.0 +/- 3.8% in the striatum and by 68.1 +/- 4.5% in the motor cortex, compared with the contralateral side (100%). DISCUSSION: This study showed that acupuncture had neuroprotective effects against focal ischemia in the middle cerebral artery occlusion model.

A novel subtelomeric translocation t(5;9) and a deletion of the RB1 gene in a patient with acute myeloid leukemia (AML-M0).

No chromosomal rearrangements have been identified as specifically associated with minimally differentiated acute myeloid leukemia (AML-M0). Several research groups studied the cytogenetic features of AML-M0 and found that as much as 81% of patients with AML-M0 had chromosomal rearrangements; primarily -5/5q- and/or -7/7q- deletions or translocations involving 12p. A patient, who was diagnosed with AML-M0 eighteen months ago, was referred for cytogenetic evaluation for possible AML relapse. A subtle, cryptic t(5;9)(q35.3;q34.3), plus a deletion of the RB1 gene were detected in 18 out of 20 cells analyzed by FISH utilizing the TelVysion assay kit. To rule out the possibility that these chromosomal changes were related to the relapse of AML in this case, we repeated the same FISH test on the specimen at initial diagnosis before any treatment. The same abnormalities were found. To our knowledge, this is the first case reported with subtelomeric t(5;9)(q35.3;q34.3) and the deletion of the RB1 gene in a patient with AML-M0. Whether the t(5;9) combined with the deletion of the RB1 gene plays an important role in the development of AML-M0 warrants further investigation.

Molecular genetic evidence of Y chromosome loss in male patients with hematological disorders.

BACKGROUND: There has been continuous debate as to whether Y chromosome loss is an age related phenomenon or a cytogenetic marker indicating a malignant change. This study aimed to investigate the frequency of Y chromosome loss in the specific patients in order to determine whether it is an age related phenomena or a cytogenetic marker indicating a malignant change. METHODS: Five hundred and ninety-two male patients with a median age of 59 years old (22 - 95 years) were included in this study. These patients were divided into two groups: the study group, including 237 patients who had hematological disorders included myeloproliferative disorder (MPD), myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), multiple myeloma (MM), and lymphoma and the control group including 355 patients with no evidence of hematological disease. Both conventional cytogenetics and fluorescence in situ hybridization using DNA probes specific for the centromere of chromosomes X or Y were performed according to our standard laboratory protocols. RESULTS: Twenty-four out of 237 patients with hematological disorders (10.1%) had Y chromosome loss. Of these 24 patients, 2 patients had AML (5.0% of all AML patients), 2 patients had CML (5.7% of all CML patients), 2 patients had MPD (8.0% of all MPD patients), 3 patients had MM (10.0% of all MM patients), 5 patients had lymphoma (10.6% of all lymphoma patients) and 10 patients had MDS (16.7% of all MDS patients). Twenty-one out of these 24 patients had a loss of Y chromosome as the sole anomaly and the remaining three had a loss of Y chromosome accompanied with other structural changes detected by conventional cytogenetic analysis. Fluorescence in situ hybridization (FISH) analysis confirmed the routine cytogenetic results. All 24 patients had a loss of Y chromosome with a range of 17.5% - 98.5% of cells. Two of the patients, one with AML and another with CML, had karyotype and FISH testing done both at the initial diagnosis and during remission. The results showed a loss of Y chromosome at initial diagnosis but a normal 46, XY karyotype during remission. Only 9 out of 355 patients (2.5%) without evidence of hematological disease had Y chromosome loss, among them 7 patients had cardiovascular diseases and 2 patients had kidney diseases. Comparison of the incidence of Y chromosome loss in patients with hematological disorders or without evidence of hematological disease using statistical analysis showed a statistically significance difference (P < 0.05). CONCLUSIONS: The present study demonstrated that the frequency of Y chromosome loss is significantly higher in patients with hematological disorders than in patients without hematological disorders, which indicates that the loss of Y chromosome is associated with a neoplastic change.

A de novo centric fission of chromosome 11 in a patient with recurrent miscarriages.

We report on a de novo centric fission of chromosome 11 in a healthy female referred for chromosome analysis due to recurrent miscarriages. Both fission products were mitotically stable. This centric fission of chromosome 11 appears to have no clinical significance for this patient other than recurrent miscarriages.