A novel phenotype of 13q12.3 microdeletion characterized by epilepsy in an Asian child: a case report

Background The microdeletion of chromosome 13 has been rarely reported. Here, we report a 14-year old Asian female with a de novo microdeletion on 13q12.3. Case presentation The child suffered mainly from two types of epileptic seizures: partial onset seizures and myoclonic seizures, accompanied with intellectual disability, developmental delay and minor dysmorphic features. The electroencephalogram disclosed slow waves in bilateral temporal, together with generalized spike-and-slow waves, multiple-spike-and-slow waves and slow waves in bilateral occipitotemporal regions. The exome sequencing showed no pathogenic genetic variation in the patient’s DNA sample. While the single nucleotide polymorphism (SNP) array analysis revealed a de novo microdeletion spanning 2.324 Mb, within the cytogenetic band 13q12.3. Conclusions The epilepsy may be associated with the mutation of KATNAL1 gene or the deletion unmasking a recessive mutation on the other allele, and our findings could provide a phenotypic expansion.

Targeting the Ribosome Biogenesis Key Molecule Fibrillarin to Avoid Chemoresistance

Background: Inherent or acquired chemo resistance in cancer patients has been a perpetual limitation in cancer treatment. Expanding knowledge on essential cellular processes opens a new window for therapeutic targeting. Ribosome biogenesis is a process that shows potential due to its fundamental role in cell development and contribution to tumorigenesis as a result of its upregulation. Inhibiting components of ribosome biogenesis has been explored and has shown interesting results. Yet, an important key component, methyltransferase Fibrillarin (FBL), which influences both the abundance and composition of ribosomes, has not been exploited thus far. Methods: In this literature review, we describe relevant aspects of ribosome biogenesis in cancer to emphasize the potential of FBL as a therapeutic target, in order to lower the genotoxic effects of anti-cancer treatment. Results: Remarkably, the amplification of the 19q13 cytogenetic band, including the gene coding for FBL, correlated to cell viability and resistance in pancreatic cells as well as to a trend toward a shorter survival in pancreatic cancer patients. : Targeting ribosome biogenesis, more specifically compared to the secondary effects of chemotherapeutics such as 5-fluorouracil or oxaliplatin, has been achieved by compound CX-5461. The cell dependent activity of this Pol I inhibitor has been reported in ovarian cancer, melanoma and leukemia models with active or mutated p53 status, presenting a promising mechanism to evade p53 resistance. Conclusion: Targeting critical ribosome biogenesis components in order to decrease the genotoxic activity in cancer cell looks promising. Hence, we believe that targeting key protein rRNA methyltransferase FBL shows great potential, due to its pivotal role in ribosome biogenesis, its correlation to an improved survival rate at low expression in breast cancer patients and its association with p53.

Rare Case of Female with Pelizaeus Mertzbacher Disease Due to Deletion of Proteolipid Protein 1

Pelizaeus Merzbacher Disease (PMD) is a rare X-linked central nervous system (CNS) disease involving the proteolipid protein 1 (PLP1) gene. Patients exhibit signs for instance nystagmus, hypotonia, ataxia. We report a three year old female patient with chief compliant of developmental delay. On physical examination, patient was alert but had poor eye contact while sitting in a stroller. Since no chromosomal evaluation was performed, a chromosomal microarray testing was performed. Review of geneticist report indicated that patient carries a deletion of at least 2.26 Mb within cytogenetic band Xq22.1 to Xq22.2 which is known to contain 39 genes. Out of the 39 genes, PLP1 is associated with known clinical disorder; PMD. Our case highlights the second only known female with PMD due to deletions of PLP1 gene. For a patient with developmental delay, the importance of performing genetic testing and/or radiological imaging early on is strongly recommended.

“KARIBIN,” an Information Resource for Obtaining Genomic Information in a Cytogenetic Band

KARIBIN (http://sgiweb.ncbi.nlm.nih.gov:80/Zjing/yac.html) is a karyotypicregion-based integrated information resource that provides a comprehensive view of the integrated mapping and sequencing data for the human genome. A cytogenetic band is linked to a genetic or physical location using fluorescence in situ hybridization (FISH) mapping data. The genetic, physical mapping data and the sequencing data are integrated using STS markers positioned on multiple maps. For each cytogenetic band, the user can obtain the most up-to-date information that includes genetic and physical maps, human transcript gene map, YAC and PAC/BAC clone coverage, disease gene phenotype, and high throughput genomic sequences from the major human genome sequencing centers. This information provides a framework for future experiments and may accelerate the process of disease gene hunting. It is envisioned that other cytogenetic-based information such as chromosome aberrations can be linked to this framework.