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)

Since the Seventh Fragile X and XLMR Mental Retardation (XLMR) Workshop in 1995, the genes for Coffin-Lowry, Mohr-Tranebjaerg, and Opitz G/BBB syndromes have been cloned. Jensen syndrome has been found to be allelic to Mohr-Tranebjaerg. Twenty new XLMR syndromes and metabolic or neuromuscular disorders have been reported. Twenty-four new localizations have been established, including five in previously reported conditions (FG, Carpenter, Arts, OPA2, and OFD1). The number of families with nonspecific XLMR that have been reported has continued to increase; 58 families or loci are now known. Eighteen new families with nonspecific mental retardation (MRX) have been reported. Two of them, however, were subsequently found to have mutations in the RABGDIA gene, which codes for a GDP-dissociation inhibitor for RAB proteins. In total, 41 more entries have been added to the X chromosome map of XLMR. The total number of known syndromes and MRX families has increased to 178. Of the 120 known XLMR disorders, 53 have been mapped, and 22 have been cloned. Assuming that at least 10 loci are necessary to account for the 58 families with MRX, the total number of XLMR loci counted so far would be 130. Although it is likely that many of the disorders will eventually prove to be allelic, it is not possible at present to determine the precise number of loci for nonspecific XLMR.
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PMID:XLMR genes: update 1998. 1020 55

We report on a large family in which a novel X-linked recessive mental retardation (XLMR) syndrome comprising macrocephaly and ciliary dysfunction co-segregates with a frameshift mutation in the OFD1 gene. Mutations of OFD1 have been associated with oral-facial-digital type 1 syndrome (OFD1S) that is characterized by X-chromosomal dominant inheritance and lethality in males. In contrast, the carrier females of our family were clinically inconspicuous, and the affected males suffered from severe mental retardation, recurrent respiratory tract infections and macrocephaly. All but one of the affected males died from respiratory problems in infancy; and impaired ciliary motility was confirmed in the index patient by high-speed video microscopy examination of nasal epithelium. This family broadens the phenotypic spectrum of OFD1 mutations in an unexpected way and sheds light on the complexity of the underlying disease mechanisms.
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PMID:A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome. 1678 69

Centriolar satellites are non-membrane cytoplasmic granules that deliver proteins to centrosome during centrosome biogenesis and ciliogenesis. Centriolar satellites are highly dynamic during cell cycle or ciliogenesis and how they are regulated remains largely unknown. We report here that sorting nexin 17 (SNX17) regulates the homeostasis of a subset of centriolar satellite proteins including PCM1, CEP131, and OFD1 during serum-starvation-induced ciliogenesis. Mechanistically, SNX17 recruits the deubiquitinating enzyme USP9X to antagonize the mindbomb 1 (MIB1)-induced ubiquitination and degradation of PCM1. SNX17 deficiency leads to enhanced degradation of USP9X as well as PCM1 and disrupts ciliogenesis upon serum starvation. On the other hand, SNX17 is dispensable for the homeostasis of PCM1 and USP9X in serum-containing media. These findings reveal a SNX17/USP9X mediated pathway essential for the homeostasis of centriolar satellites under serum starvation, and provide insight into the mechanism of USP9X in ciliogenesis, which may lead to a better understating of USP9X-deficiency-related human diseases such as X-linked mental retardation and neurodegenerative diseases.
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PMID:SNX17 Recruits USP9X to Antagonize MIB1-Mediated Ubiquitination and Degradation of PCM1 during Serum-Starvation-Induced Ciliogenesis. 3167 55