Genotype-phenotype analysis of human frontoparietal polymicrogyria syndromes

Università di Pisa, Pisa, Tuscany, Italy
Annals of Neurology (Impact Factor: 11.91). 11/2005; 58(5):680-7. DOI: 10.1002/ana.20616
Source: PubMed

ABSTRACT Human cerebral cortical polymicrogyria is a heterogeneous disorder, with only one known gene (GPR56) associated with an apparently distinctive phenotype, termed bilateral frontoparietal polymicrogyria (BFPP). To define the range of abnormalities that could be caused by human GPR56 mutations and to establish diagnostic criteria for BFPP, we analyzed the GPR56 gene in a cohort of 29 patients with typical BFPP. We identified homozygous GPR56 mutations in all 29 patients with typical BFPP. The total of 11 GPR56 mutations found represented a variety of distinct founder mutations in various populations throughout the world. In addition, we analyzed five patients with BFPP who did not show GPR56 mutation and found that they define a clinically, radiographically, and genetically distinct syndrome that we termed BFPP2. Finally, we studied seven patients with a variety of other polymicrogyria syndromes including bilateral frontal polymicrogyria, bilateral perisylvian polymicrogyria, and bilateral generalized polymicrogyria. No GPR56 mutation was found in these patients. This study provides a molecular confirmation of the BFPP phenotype and provides the wherewithal for diagnostic screening.

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Available from: William Dobyns, Oct 05, 2014
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    • "Bilateral frontal and frontoparietal polymicrogyria (BFPP) have been reported in sporadic patients and in recessive pedigrees (Guerrini et al., 2000; Piao et al., 2005). BFPP has been reported in several consanguineous and nonconsanguineous families and has been associated with mutations of the G protein–coupled receptor gene 6 (GPR56) (Piao et al., 2005). The topography of the cortical abnormality, as well as the pattern of expression of mouse Gpr56, suggest that GPR56 regulates cortical patterning. "
    Epilepsia 02/2010; 51 Suppl 1:10-2. DOI:10.1111/j.1528-1167.2009.02434.x · 4.58 Impact Factor
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    • "BFPP seems to be genetically homogeneous, since all families reported to date show an AR pattern and association with mutations in the GPR56 gene. Patients with BFPP2, on the other hand, do not have a mutation in the GPR56 gene (Piao et al., 2005). The GPR56 protein is an adhesion G protein–coupled receptor. "
    Epilepsia 02/2010; 51 Suppl 1:13-6. DOI:10.1111/j.1528-1167.2009.02435.x · 4.58 Impact Factor
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    • "Polymicrogyria is a developmental cortical malformation associated with dyslexia (Taylor et al. 2001; Clark et al. 2000; Clark and Plante 1998; Galaburda and Eidelberg 1982) and epilepsy (Kim et al. 2006; Crino 2004; Segawa et al. 1979) that has a varied etiology, including genetic and acquired causes (Chang et al. 2006; Cantagrel et al. 2006; Piao et al. 2005; Mitchell et al. 2003; Iannetti et al. 1998; Barkovich et al. 1995; Barkovich and Lindan 1994; Richman et al. 1974). Despite identification of genes contributing to some forms of polymicrogyria, including GPR56, PAX6, and AH11 (Guerrini and Marini 2006; Piao et al. 2005; Gleeson et al. 2004; Mitchell et al. 2003), the connection between the structural abnormality and neurological dysfunction is ill-understood. These genes play a role in neuronal migration and differentiation (Fukumitsu et al. 2006; Shashidhar et al. 2005; Tzoulaki et al. 2005; Little et al. 2004). "
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    ABSTRACT: Structural malformations of the cortex, arising as a result of genetic mutation or injury during development are associated with dyslexia, epilepsy, and other neurological deficits. We have used a rat model of a microgyral malformation to examine mechanisms of epileptogenesis. Our previous studies showed that the frequency of miniature excitatory postsynaptic currents (mEPSCs) recorded in neocortical layer V pyramidal neurons is increased in malformed cortex at a time when field potential epileptiform events can be evoked. Here we show that the increase occurs at an age before onset of cortical epileptiform activity and at a time when the frequency of mEPSCs in control layer V pyramidal neurons is stable. An increase in the frequency of spontaneous (s)EPSCs in layer V pyramidal neurons of malformed cortex occurs earlier than that for mEPSCs, suggesting that there may additionally be alterations in intrinsic properties that increase the excitability of the cortical afferents. Frequencies of EPSC bursts and late evoked activity were also increased in malformed cortex. These results suggest that a hyperinnervation of layer V pyramidal neurons by excitatory afferents occurs as an active process likely contributing to subsequent development of field epileptiform events.
    Journal of Neurophysiology 08/2007; 98(1):178-86. DOI:10.1152/jn.00106.2007 · 3.04 Impact Factor
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