Article

A novel mutation in the PHF8 gene is associated with X-linked mental retardation with cleft lip/cleft palate.

Center for Molecular Studies, J C Self Research Institute, Greenwood Genetic Center, Greenwood, SC 29646, USA.
Clinical Genetics (Impact Factor: 3.65). 08/2007; 72(1):19-22. DOI: 10.1111/j.1399-0004.2007.00817.x
Source: PubMed

ABSTRACT Recently, two truncating mutations in the PHF8 (plant homeodomain finger protein 8) gene have been found to cause X-linked mental retardation associated with cleft lip/cleft palate (CL/P). One of the truncating mutations was found in the original family with Siderius-Hamel CL/P syndrome where only two of the three affected individuals had mental retardation (MR) with CL/P and one individual had mild MR. The second mutation was present in a family with four affected men, three of whom had MR and CL/P, while the fourth individual had mild MR without clefting. Here, we report a novel nonsense mutation (p.K177X) in a male patient who has MR associated with CL/P. The mutation results in a truncated PHF8 protein lacking the Jumonji-like C terminus domain and five nuclear localization signals. Our finding further supports the hypothesis that the PHF8 protein may play an important role in cognitive function and midline formation.

Download full-text

Full-text

Available from: Fatima Abidi, Jul 04, 2015
0 Followers
 · 
95 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetic chromatin remodeling, including reversible histone methylation, regulates gene transcription in brain development and synaptic plasticity. Aberrant chromatin modifications due to mutant chromatin enzymes or chemical exposures have been associated with neurological or psychiatric disorders such as mental retardation, schizophrenia, depression, and drug addiction. Some chromatin enzymes, such as histone demethylases JARID1C and UTX, are coded by X-linked genes which are not X-inactivated in females. The higher expression of JARID1C and UTX in females could contribute to sex differences in brain development and behavior.
    Hormones and Behavior 03/2011; 59(3):383-92. DOI:10.1016/j.yhbeh.2010.08.019 · 4.51 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Methylation of histone H3 Lys 9 and Lys 27 (H3K9 and H3K27) is associated with transcriptional silencing. Here we show that KDM7, a JmjC domain-containing protein, catalyzes demethylation of both mono- or dimethylated H3K9 and H3K27. Inhibition of KDM7 orthologs in zebrafish resulted in developmental brain defects. KDM7 interacts with the follistatin gene locus, and KDM7 depletion in mammalian neuronal cells suppressed follistatin gene transcription in association with increased levels of dimethylated H3K9 and H3K27. Our findings identify KDM7 as a dual demethylase for H3K9 and H3K27 that functions as an eraser of silencing marks on chromatin during brain development.
    Genes & development 03/2010; 24(5):432-7. DOI:10.1101/gad.1864410 · 12.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetic modifications are heritable chromatin alterations that contribute to the temporal and spatial interpretation of the genome. The epigenetic information is conveyed through a multitude of chemical modifications, including DNA methylation, reversible modifications of histones, and ATP-dependent nucleosomal remodeling. Deregulation of the epigenetic machinery contributes to the development of several pathologies, including cancer. Chromatin modifications are multiple and interdependent and they are dynamically modulated in the course of various biological processes. Combinations of chromatin modifications give rise to a complex code that is superimposed on the genetic code embedded into the DNA sequence to regulate cell function. This review addresses the role of epigenetic modifications in cancer, focusing primarily on histone methylation marks and the enzymes catalyzing their removal.
    Advances in Cancer Research 02/2009; 102:103-69. DOI:10.1016/S0065-230X(09)02004-1 · 4.26 Impact Factor