No Evidence of Abnormal Expression of Beta-Catenin and Bcl-2 Proteins in Pilomatricoma as One Clinical Feature of Tetrasomy 9p Syndrome

Background. Little is currently known about the genetics of pilomatricoma. A number of studies have reported some evidence that this disease may have a genetic association with mutations of CTNNB1 gene or expression of the beta-catenin protein. In this study, we reviewed literatures involving 30 patients with various genetic syndromes that have been linked to pilomatricoma and found that somatic mutations of the CTNNB1 gene were reported in 67% of patients. Pilomatricoma has been reported in patients with chromosome 9 rearrangements, including 4 patients with tetrasomy 9p syndrome and one patient with partial trisomy 9. In addition to beta-catenin, the expression of bcl2 was observed in pilomatricoma. Objectives. To report an additional case of tetrasomy 9p syndrome with concurrent pilomatricoma and to examine whether abnormal protein expressions of the CTNNB1 and/or BCL2 genes were present. Methods. Cytogenetic analysis was carried out on peripheral blood, biopsied skin, and pilomatricoma tissue obtained from a patient with tetrasomy 9p syndrome. Immunohistochemical staining was performed on the pilomatricoma tissue, using beta-catenin and bcl2 monoclonal antibodies. Results. SNP microarray revealed nonmosaic gain of the short arm of chromosome 9. A nonmosaic isodicentric chromosome 9 was identified in the peripheral blood but this rearranged chromosome was detected in only 8.3% of the skin fibroblasts. Chromosomal abnormalities were not detected in the pilomatricoma nor expression of beta-catenin or bcl2 proteins in our patient. Conclusion. Pilomatricoma could be a new clinical feature associated with tetrasomy 9p syndrome; however, we found no evidence of tetrasomy 9p or abnormal beta-catenin or bcl2 proteins of the CTNNB1 and BCL2 genes in our pilomatricoma patient.

The Effectiveness of Perampanel for Myoclonic Seizures in Down Syndrome with Isodicentric Chromosome 21

Epileptic seizures are common in the elderly Down syndrome population. We encountered a patient with Down syndrome in whom karyotyping showed the rare isodicentric chromosome 21 and who suffered from myoclonic seizures. A 52-year-old woman with Down syndrome experienced sudden onset of drowsiness and frequent myoclonic jerks in the upper body. Video-EEG recordings demonstrated generalized polyspike-wave discharges consistent with myoclonic jerks, which were exacerbated by photo-stimulation. Her myoclonus completely resolved with perampanel administration. Perampanel was effective for myoclonic seizures in our patient. We suggest that perampanel is an option as first-line therapy for epilepsy and myoclonus in elderly Down syndrome patients.

Selective Advantage of the Recurrent Isodicentric Chromosome 20 in Myeloid Disease

Interstitial deletion of the long arm of chromosome 20 is a common genomic imbalance associated with myeloid hematologic disorders. Originally identified by conventional cytogenetics and fluorescent in situ hybridization, it has been hypothesized that deletion of 20q results in haploinsuffciency of tumor suppressor gene(s) causing a proliferative advantage. The advent of microarray analysis has revolutionized the detection of copy number gains and losses associated with a variety of oncogenic mechanisms. Initial studies using microarray analysis have shown significant heterogeneity in the breakpoints associated with interstitial deletions of 20q, ruling out the possibility of a recurrent genomic fusion, but establishing a critical region which appears to support a tumor suppressor gene loss model. We have documented six individuals, referred for microarray analysis of myelodysplasia, with alterations of chromosome 20 involving a similar complex rearrangement. The rearrangement is an isodicentric chromosome 20 consisting of 1) a deletion of the majority of the short arm pter to p11.1, 2) retention of the region flanking the centromere from p11.1 to q11.21, and 3) an adjacent interstitial deletion of the long arm that can vary in size similar to the common 20q deletion. The breakpoints of the region flanking the centromere at 20p11.1 are within a block of segmental repeats and virtually identical in all 6 cases while the break points in 20q11.21 are within ~1.1 MB (30,785,977-31,887,129). In addition, one of the six cases shows additional copies of the region flanking the centromere from p11.1 to q11.21 consistent with supernumerary marker chromosomes found by conventional cytogenetics. These results suggest that there is a selective advantage associated with a gene(s) within the chromosome 20p11.1->q11.21 segment. The PDRG1 gene is localized to 20q11.21and has been shown to be upregulated in number of malignant cell types including colon, rectum, ovary, lung, stomach, breast and uterus. As our results show, PDRG1 is duplicated or amplified in all 6 cases with the isodicentric chromosome 20. Therefore, these results suggest PDRG1 upregulation may contribute to the pathogenicity of myelodysplasia by conferring a selective advantage in individuals with the isodicentric chromosome 20. Disclosures No relevant conflicts of interest to declare.