Chromosome 12q24.31-q24.33 deletion causes multiple dysmorphic features and developmental delay: First mosaic patient and overview of the phenotype related to 12q24qter defects

<p>Abstract</p> <p>Background</p> <p>Genomic imbalances of the 12q telomere are rare; only a few patients having 12q24.31-q24.33 deletions were reported. Interestingly none of these were mosaic. Although some attempts have been made to establish phenotype/genotype interaction for the deletions in this region, no clear relationship has been established to date.</p> <p>Results</p> <p>We have clinically screened more than 100 patients with dysmorphic features, mental retardation and normal karyotype using high density oligo array-CGH (aCGH) and identified a ~9.2 Mb hemizygous interstitial deletion at the 12q telomere (Chromosome 12: 46,XY,del(12)(q24.31q24.33) in a severely developmentally retarded patient having dysmorphic features such as low set ears, microcephaly, undescended testicles, bent elbow, kyphoscoliosis, and micropenis. Parents were found to be not carriers. MLPA experiments confirmed the aCGH result. Interphase FISH revealed mosaicism in cultured peripheral blood lymphocytes.</p> <p>Conclusions</p> <p>Since conventional G-Banding technique missed the abnormality; this work re-confirms that any child with unexplained developmental delay and systemic involvement should be studied by aCGH techniques. The FISH technique, however, would still be useful to further delineate the research work and identify such rare mosaicism. Among the 52 deleted genes, <it>P2RX2, ULK1, FZD10, RAN, NCOR2 STX2, TESC, FBXW8</it>, and <it>TBX3 </it>are noteworthy since they may have a role in observed phenotype.</p

Genomic and transcriptomic analyses distinguish classic Rett and Rett-like syndrome and reveals shared altered pathways

AbstractRett syndrome (RTT) is an X-linked neurodevelopmental disorder characterized by derangements in nervous system especially in cognition and behavior. The present study aims to understand the molecular underpinnings of two subtypes of RTT, classic RTT and Rett-like, and to elucidate common pathways giving rise to common RTT phenotype using genomic and transcriptomic approaches. Mutation screening on selected nuclear genes revealed only MECP2 mutations in a subset of classic RTT patients. MLPA assays and mtDNA screenings were all negative. Genome-wide copy number analysis indicated a novel duplication on X chromosome. Transcriptional profiling revealed blood gene signatures that clearly distinguish classic RTT and RTT-like patients, as well as shared altered pathways in interleukin-4 and NF-κB signaling pathways in both subtypes of the syndrome. To our knowledge, this is the first report on investigating common regulatory mechanisms/signaling pathways that may be relevant to the pathobiology of the “common RTT” phenotype