Rubinstein-Taybi syndrome

Abbreviations CBP, CREB binding protein CREB, cAMP response element binding protein FAT, factor acetyltransferase HAT, histone acetyltransferase MEL, mixed lineage leukaemia protein MORE, MOZ related factor MOZ, monocytic leukaemia zinc finger protein PHD, plant homeodomain RTS, Rubinstein-Taybi syndrome, TIE, transcription intermediary factor... 

Petrij F, Dorsman JC, Dauwerse HG, Giles RH, Peelers T, Hennekam RC, Breuning MH, Peters DJ (2000b) Rubinstein-Taybi syndrome caused by a De Novo reciprocal translocation t(2 16)(q36.3 pl3.3). Am J Med Genet 92 47-52... 

Tanaka Y, Naruse I, Maekawa T, Masuya H, Shiroishi T, Ishu S (1997) Abnormal skeletal patterning in embryos lacking a single Cbp allele a partial similarity with Rubinstein-Taybi syndrome. Proc Natl... 

Figure 3. The many ways to lose a HAT. Decreased amounts of functional CBP protein and subsequent CBP s loss of function has been observed in different contexts of neurological disorders and neuronal apoptosis. RTS (Rubinstein-Taybi Syndrome) results from a mutation on one cbp gene allele. In several cases of polyQ diseases, CBP can be sequestred by the mutated polyQ proteins, forming aggregates in the cytoplasm or the nucleus. CBP proteasomal degradation was also shown to be favored by polyQ proteins. CBP is a caspase-6 substrate in cerebellar granule neurons (CGN) deprived of potassium modeling caspase-dependent apoptosis. Finally, cbp gene repression has been observed in oxidative stress-induced death of a motomeuronal cell line. The mechanisms by which CBP levels are reduced in motomeurons of ALS mice is still unknown...

Alarcon JM, Malleret G, Touzani K, Vronskaya S, Ishii S, Kandel ER, Barco A (2004) Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron 42(6) 947-959 Alnernri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J (1996) Human lCElCED-3 protease nomenclature. Cell 87(2) 171... 

Kalkhoven E (2004) CBP and p300 HATS for different occasions. Biochem Pharmacol 68(6) 1145-1155 Kalkhoven E, Roelfsema JH, Teunissen H, den Boer A, Ariyurek Y, Zantema A, Breuning MH, Hennekam RC, Peters DJ (2003) Loss of CBP acetyltransferase activity by PHD finger mutations in Rubinstein-Taybi syndrome. Hum Mol Genet 12(4) 441 50... 

Miller RW, Rubinstein JH (1995) Tumors in Rubinstein-Taybi syndrome. Am J Med Genet 56(1) 112-115... 

Deletion/Point mutation Rubinstein-Taybi syndrom... 

Taki T, Sako M, Tsuchida M, Hayashi Y (1997) The t(ll 16)(q23 pl3) translocation in Myelodysplastic syndrome fuses the MLL gene to the CBP gene. Blood 89 3945—3950 Tanaka Y, Naruse I, Maekawa T, Masuya H, Shiroishi T, Ishii S (1997) Abnormal skeletal patterning in embryos lacking a single Cbp allele A partial similarity with Rubinstein-Taybi syndrome. Proc Natl Acad Sci USA 94 10215-10220... 

In 1963 J.H. Rubinstein and H. Taybi reported a rare human disease that induced mental retardation, an increased risk of neoplasia and physical abnormalities, including broad thumbs, big and broad toes, short stature and craniofacial anomalies. The molecular basis of the Rubinstein-Taybi syndrome (RTS) was later discovered to be a disruption of one copy of the human CREB binding protein (CBP or CREB-BP) gene that encodes the histone acetyltransferase CBP [3]. In addition to CBP, all mammals have a closely related acetyltransferase, p300. Retrospectively, RTS was the first disease found to be due to a defective acetylation process [1-3]. 

Masuno, M. et al. (1995) Rubinstein-Taybi-syndrome caused by mutations in the transcriptional co-activator GBP. Nature, 376, 348-351. 

Alarcon JM et al (2004) Chromatin acetylation, memory, and LTP are impaired in CBP+/— mice a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron 42(6) 947-959... 

Rubinstein-Taybi syndrome Broad thumbs and toes, distinctive facial features, mental retardation, microcephaly, cryptorchism, small phallus Microdeletion 16p (about 25%), most often de novo, further cases with mutations in CREBBP, EP300... 

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