A novel mutation in MED12 causes FG syndrome (Opitz–Kaveggia syndrome)

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Clinical Genetics (Impact Factor: 3.93). 02/2011; 79(2):183-8. DOI: 10.1111/j.1399-0004.2010.01449.x
Source: PubMed


Rump P, Niessen RC, Verbruggen KT, Brouwer OF, de Raad M, Hordijk R. A novel mutation in MED12 causes FG syndrome (Opitz–Kaveggia syndrome).
Opitz–Kaveggia syndrome is a rare X-linked multiple congenital anomalies and intellectual disability disorder caused by the recurrent p.R961W mutation in the MED12 gene. Twenty-three affected males from 10 families with this mutation in the MED12 gene have been described so far. Here we report on a new family with three affected cousins, in which we identified a novel MED12 mutation (p.G958E). This is the first demonstration that other mutations in this gene can also lead to Opitz–Kaveggia syndrome. The clinical phenotype of these three new cases is reviewed in detail and compared with the previous reported cases.

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    • "Exclusion criteria include female sex, lack of intellectual disability, and autosomal patterns of inheritance. One family who met these criteria was found to carry a novel p. G958E mutation in MED12, with mild manifestations in carrier females [Rump et al., 2011]. "
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    ABSTRACT: MED12: is a member of the large Mediator complex, which has a critical and central role in RNA polymerase II transcription. As a multiprotien complex, Mediator regulates signals involved in cell growth, development, and differentiation, and it is involved in a protein network required for extraneuronal gene silencing and also functions as a direct suppressor of Gli3-dependent Sonic hedgehog signaling. This may explain its role in several different X-linked intellectual disability syndromes that share some overlapping clinical features. This review will compare and contrast four different clinical conditions that have been associated with different mutations in MED12, which is located at Xq13. To date, these conditions include Opitz-Kaveggia (FG) syndrome, Lujan syndrome, Ohdo syndrome (Maat-Kievit-Brunner type, or OSMKB), and one large family with profound X-linked intellectual disability due to a novel c.5898insC frameshift mutation that unlike the other three syndromes, resulted in affected female carriers and truncation of the MED12 protein. It is likely that more MED12 mutations will be detected in sporadic patients and X-linked families with intellectual disability and dysmorphic features as exome sequencing becomes more commonly utilized, and this overview of MED12-related disorders may help to correlate MED12 genotypes with clinical findings. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · Oct 2013 · American Journal of Medical Genetics Part A
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