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)

Renpenning syndrome represents a prototypic X-linked mental retardation condition with full expression of the phenotype in males and little or no expression in females. The predominant clinical findings are microcephaly, long narrow face, short stature with lean body build, and small testes. Mental retardation, usually of severe degree, occurs in 95% of cases. Less than 20% of cases have major malformations, the most common being cardiac defects and cleft palate. Subsequent to the description of mutations in the polyglutamine tract binding protein 1 (PQBP1) in Sutherland-Haan syndrome, Hamel cerebropalatocardiac syndrome, MRX55, and two small XLMR families, a single nucleotide insertion has been found in the original family with Renpenning syndrome and an AGAG deletion in a second family with the Renpenning syndrome. Mutations have also been found in Golabi-Ito-Hall syndrome, Porteous syndrome, and an additional small family. It is now demonstrated that five named XLMR syndromes (Sutherland-Haan, Hamel cerebropalatocardiac, Golabi-Ito-Hall, Porteous, and Renpenning), one nonsyndromic family (MRX55), and three small XLMR families have PQBP1 mutations and are thus allelic XLMR entities. In acknowledgement of the historical importance of the original report of Renpenning syndrome [1962], we propose that the entities with PQBP1 mutations be combined under the name of Renpenning syndrome.
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PMID:Renpenning syndrome comes into focus. 1578 10

The PQBP1 (polyglutamine tract-binding protein 1) gene encodes a nuclear protein that regulates pre-mRNA splicing and transcription. Mutations in the PQBP1 gene were reported in several X chromosome-linked mental retardation disorders including Golabi-Ito-Hall syndrome. The missense mutation that causes this syndrome is unique among other PQBP1 mutations reported to date because it maps within a functional domain of PQBP1, known as the WW domain. The mutation substitutes tyrosine 65 with cysteine and is located within the conserved core of aromatic amino acids of the domain. We show here that the binding property of the Y65C-mutated WW domain and the full-length mutant protein toward its cognate proline-rich ligands was diminished. Furthermore, in Golabi-Ito-Hall-derived lymphoblasts we showed that the complex between PQBP1-Y65C and WBP11 (WW domain-binding protein 11) splicing factor was compromised. In these cells a substantial decrease in pre-mRNA splicing efficiency was detected. Our study points to the critical role of the WW domain in the function of the PQBP1 protein and provides an insight into the molecular mechanism that underlies the X chromosome-linked mental retardation entities classified globally as Renpenning syndrome.
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PMID:Y65C missense mutation in the WW domain of the Golabi-Ito-Hall syndrome protein PQBP1 affects its binding activity and deregulates pre-mRNA splicing. 2041 Mar 8