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

• Published in: Genomics (San Diego, Calif.) Vol. 97; no. 1; pp. 19 - 28
• Main Authors: Colak, Dilek, Al-Dhalaan, Hesham, Nester, Michael, AlBakheet, AlBandary, Al-Younes, Banan, Al-Hassnan, Zohair, Al-Dosari, Mohammad, Chedrawi, Aziza, Al-Owain, Muhammad, AbuDheim, Nada, Al-Alwan, Laila, Al-Odaib, Ali, Ozand, Pinar, Inan, Mehmet Sait, Kaya, Namik
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 2011; Elsevier
• Subjects: Biological and medical sciences; CDKL5; Copy number; Diagnosis, Differential; Diverse techniques; FOXG1; Functional pathway analysis; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Genes related to Rett phenotype; Genes. Genome; Genetics of eukaryotes. Biological and molecular evolution; Genome-wide gene expression profiling; Genomics; Humans; MBD2; MECP2; Microarray; Molecular and cellular biology; Molecular genetics; mtDNA sequencing; Mutation; Mutation analysis; NTNG1; Phenotype; Rett; Rett Syndrome - diagnosis; Rett Syndrome - genetics; Rett-like; RTT; Signal Transduction; NTNG1; CDKL5; Rett-like; Copy number; FOXG1; MBD2; Microarray; Genome-wide gene expression profiling; mtDNA sequencing; MECP2; Functional pathway analysis; RTT; Rett; Mutation analysis; Genes related to Rett phenotype; Genomics; Mitochondrial DNA; Gene; Transcriptomics; Degenerative disease; Sequencing; Nervous system diseases; Genetic disease; Cerebral disorder; Gene expression profile; Phenotype; Central nervous system disease; Rett syndrome; Mutation
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2010.09.004

Rett 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.