Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rubinstein-Taybi syndrome (RTS) is a rare syndrome with a frequency of approximately 1 in 125,000 affected newborns, which is characterized by mental retardation, growth retardation, a particular dysmorphology and, in a subset of cases, immunodeficiency. RTS is typically caused by CREBBP deficiency, and heterozygous mutation or deletion of the CREBBP gene has been identified in 60-70% of patients. The inheritance is autosomal dominant but reports of vertical transmission are exceedingly rare; near-all cases are caused by de novo mutations. Here we present an 8-month-old boy with varicella meningoencephalitis, RTS, and a de novo deletion of the CREBBP gene of two base pairs at position 201-202 in exon 2, c. 201 202delT. The mutation has not been described previously but it predicts a protein truncation, and truncating CREBBP mutations are typical causes of RTS.
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PMID:Rubinstein-Taybi syndrome and CREBBP c.201 202delTA mutation: a case presenting with varicella meningoencephalitis. 1985 32

The Rubinstein-Taybi syndrome (RTS; OMIM 180849) is a well-defined mental retardation/multiple congenital anomalies (MR/MCA) syndrome characterized by postnatal growth retardation, microcephaly, specific facial features, broad thumbs and halluces, and MR of variable degree. Ten percent of patients with RTS have a microdeletion 16p13.3, 40-50% carry a mutation of the CREBBP gene and another 3% have a mutation in the EP300 gene. In the remaining patients with clinically suspected RTS no mutation can be detected. Here we describe two patients with an RTS phenotype, one with a mutation in the CREBBP gene and the other without a detectable CREBBP or EP300 mutation and without a chromosomal imbalance on high-resolution arrays. Both patients present with the characteristic facial RTS phenotype, broad thumbs and big toes, mild MR, formation of keloids and glaucoma, but without postnatal growth retardation or microcephaly. In addition, they have both congenital camptodactyly of third (and fourth) fingers, which has not reported in RTS previously. We suggest that they represent a clinical subtype of RTS.
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PMID:Two adults with Rubinstein-Taybi syndrome with mild mental retardation, glaucoma, normal growth and skull circumference, and camptodactyly of third fingers. 1993 80

Rubinstein-Taybi syndrome (RTS) is characterized by mental retardation, broad thumbs and great toes and a recognizable craniofacial phenotype. Causative mutations have been described in the CREBBP and EP300 genes. Here we present a 19-year-old woman and an unrelated 3-year-old boy, both with broad thumbs and halluces, but with facial aspects distinct from those of typical RTS. The woman had a marked learning disability, but no mental retardation. We identified a de novo c.7100delC mutation in EP300 (which predicts p.P2366RfsX35) in the woman and an apparently de novo c.638delG mutation in the boy, which predicts p.G213EfsX6. Mutations in EP300 are a known but rare cause of RTS. Only five other patients have been reported. We propose that individuals with EP300 mutations may exhibit a slightly different phenotype compared to individuals with CREBBP mutations, with milder cognitive impairment, more pronounced microcephaly, absent or mild downslanting of palpebral fissures, distinct arched eyebrows, and greater degree of retrognathia.
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PMID:Two patients with EP300 mutations and facial dysmorphism different from the classic Rubinstein-Taybi syndrome. 2094 5

Rubinstein-Taybi syndrome (RSTS), a developmental disorder comprising abnormalities that include mental retardation, an unusual facial appearance, broad thumbs and big toes is frequently associated with molecular lesions in the CREB-binding protein gene, CREBBP. The objective of the present study was to identify and analyse CREBBP mutations in Indian RSTS patients on which there are no data. Direct sequencing of CREBBP performed in 13 RSTS patients identified the three zinc fingers (CH1, CH2, CH3) and HAT domain as mutational hotspots in which ten novel pathogenic mutations were localized. Functional analysis revealed that three of these mutations affecting amino acids Glu1459, Leu1668 and Glu1724 were critical for histone acetyltransferase activity. Twenty-eight novel CREBBP single-nucleotide polymorphisms (SNPs) were also identified in the Indian population. Linkage disequilibrium studies revealed associations between (i) SNP (rs129974/c.3836-206G greater than C) and mutation (p.Asp1340Ala); (ii) (rs130002) with mutation (p.Asn435Lys) and (iii) SNPs rs129974, rs130002 and SNP (c.3836-206G greater than C) signifying a disease affection status. In conclusion, the present study reports the highest detection rate of CREBBP mutations (76.9%) in RSTS patients to date, of which ten are predicted to be pathogenic and three critical for histone acetyltransferase activity. Moreover, identification of the association of CREBBP polymorphisms with disease susceptibility could be an important risk factor for the pathogenesis of RSTS.
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PMID:Spectrum of CREBBP mutations in Indian patients with Rubinstein-Taybi syndrome. 2068 75

Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant genetic disorder and is characterized by mental retardation, distinctive facial features, broad and often angulated thumbs and great toes. We report on a 7 year old boy with classical Rubinstein-Taybi syndrome. His facial and clinical features were very typical, including broad thumbs with radial angulation and broad great toes. Rigorous genetic analysis of the CREBBP and EP300 genes using DNA sequencing and multiple ligation-dependent probe amplification (MLPA) revealed no causative mutation in this boy, only a hitherto unreported but paternally inherited heterozygous sequence alteration, c.506 1+9C>T in IVS 30-31, which most likely represents a normal variant (NetGene 2 splice prediction software). We question if this boy could have a hitherto undetectable mutation type.
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PMID:A boy with classical Rubinstein-Taybi syndrome but no detectable mutation in the CREBBP and EP300 genes. 2230 93

Rubinstein-Taybi syndrome is an autosomal dominant disorder with multiple congenital anomalies and genetic heterogeneity. Clinical manifestations include mental retardation, postnatal growth deficiency, microcephaly, broad thumbs and halluces, and characteristic facial features. Mutations in the gene encoding the transcriptional coactivator CREB-binding protein (CREBBP; OMIM 600140) on chromosome 16p13, account for about 50% to 70% of patients. Most of CREBBP mutations are de novo and the rate of recurrence in a family is low. Families with several affected children are extremely rare. We report here a Moroccan family with two children with RSTS and apparently unaffected parents. The molecular studies showed a heterozygous mutation c.4361T>A (p.Leu1454His) in exon 26 of the CREBBP gene in the two affected siblings. Neither the parents, nor the healthy brother, carry this mutation in hematologic cells. The mutation was also absent in buccal epithelial cells of both parents. We discuss the hypothesis of germinal mosaicism. This concept is very important because it complicates genetic counseling of this family who has a risk of recurrence of the mutation in subsequent pregnancies.
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PMID:Germline mosaicism in Rubinstein-Taybi syndrome. 2335 94

Rubinstein-Taybi syndrome (RTS) is an incurable genetic disorder with combination of mental retardation and physical features including broad thumbs and toes, craniofacial abnormalities, and growth deficiency. While the autosomal dominant mode of transmission is limitedly known, the majority of cases are attributable to de novo mutations in RTS. The first identified gene associated with RTS is CREB-binding protein (CREBBP/CBP). Alterations of the epigenetic 'histone code' due to dysfunction of the CBP histone acetyltransferase activity deregulate gene transcriptions that are prominently linked to RTS pathogenesis. In this review, we discuss how CBP mutation contributes to modifications of histone and how histone deacetylase inhibitors are therapeutically applicable to epigenetic conditioning in RTS. Since most genetic mutations are irreversible and therapeutic approaches are limited, therapeutic targeting of reversible epigenetic components altered in RTS may be an ideal strategy. Expeditious further study on the role of the epigenetic mechanisms in RTS is encouraged to identify novel epigenetic markers and therapeutic targets to treat RTS.
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PMID:Epigenetic mechanisms of Rubinstein-Taybi syndrome. 2438 Nov 14

Rubinstein-Taybi syndrome is characterized by distinctive facial and limb features and is associated with several types of tumors. A 29-yr-old woman with this syndrome presented with a large, complex ovarian mass. She was subsequently diagnosed with a low-grade serous carcinoma of the ovary and an endometrioid adenocarcinoma of the uterus. Rubinstein-Taybi syndrome is an autosomal dominant, multiple congenital anomalies-mental retardation syndrome. Two genes, CREBBP and EP300, have been found to be associated with this disorder, although some cases do not have an identifiable cause. These genes code for proteins that acetylate histone tails, an epigenetic modification that serves to control transcription. They also serve as cofactors to several transcription factors and modulate p53. Although these patients have a predisposition to benign and malignant neoplasms, no malignant gynecologic neoplasm has been described thus far. Although no significant evidence linking CREBBP and EP300 to gynecologic malignancies has yet been found, some studies have suggested that hypoacetylation of histones may be involved in endometrial and ovarian carcinomas.
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PMID:Synchronous ovarian and endometrial carcinomas in a patient with Rubinstein-Taybi syndrome: a case report and literature review. 2567 81


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