Abidi FE, Miano MG, Murray JC, Schwartz CE.. A novel mutation in the PHF8 gene is associated with X-linked mental retardation with cleft lip/cleft palate. Clin Genet 72: 19-22

Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States
Clinical Genetics (Impact Factor: 3.93). 08/2007; 72(1):19-22. DOI: 10.1111/j.1399-0004.2007.00817.x
Source: PubMed


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.

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Available from: Fatima Abidi
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    • "PHF8 preferentially acts on H3K9me2 and H3K9me1 (however, some results also suggest that it can demethylate H4K20me1) and associates with transcriptional activation and retinoic acid signaling pathway in neuronal differentiation (Qiu et al., 2010). Mutations in the PHF8 gene are found in patients with X-linked mental retardation (XLMR), and knockdown of PHF8 homolog leads to brain defects in zebrafish (Abidi et al., 2007; Koivisto et al., 2007; Laumonnier et al., 2005), revealing its potential involvement in human disease. "
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    • "These proteins contain an N-terminal PHD and a Jumonji-C (JmjC) domain (7). Deletions and point mutations in the PHF8 JmjC domain lead to Siderius–Hamel syndrome, mild XLMR with cleft lip and/or a cleft palate (CL/P) (4,8–10). "
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    • "Mutations in TBX22 have also been identified in patients with isolated CPO [51], [52]. As to PHF8, mutations in this gene cause the X-linked mental retardation syndrome Siderius that includes cleft palate as a common phenotypic feature [53], [54]. PHF8 is a histone lysine transcription activator expected to have a wide range of functions. "
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