Clinical variation of Aarskog syndrome in a large family with 2189de1A in the FGD1 gene

The Genetics Institute, Ha'Emek Medical Center, Afula, Israel.
American Journal of Medical Genetics Part A (Impact Factor: 2.05). 01/2006; 140(2):162-5. DOI: 10.1002/ajmg.a.31033
Source: PubMed

ABSTRACT The clinical diagnosis of ASS (Aarskog-Scott syndrome or Faciogenital Dysplasia) was made in seven individuals belonging to a large Arabic family, which was supported by molecular studies revealing a 2189delA mutation in exon 15 of the FDG1 gene. The affected individuals in this family demonstrated clinical variability particularly in their cognitive skills, raising the question whether other genetic factors might be involved in the phenotypic evolution of ASS.

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    • "FGD1 specifically activates Cdc42, which is a Rho GTPase central to signaling pathways that are important for cytoskeleton organization and embryogenesis (Gorski et al., 2000). Almost equal numbers of missense and nonsense mutations of FGD1 have been described (Orrico et al., 2000; Schwartz et al., 2000; Lebel et al., 2002; Orrico et al., 2004; Orrico et al., 2005; Kaname et al., 2006; Shalev et al., 2006; Bedoyan et al., 2009; Orrico et al., 2010), and marked allelic and phenotypic heterogeneity is evident in AAS patients with proven FGD1 mutations. "
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    • "These results imply a potential oncogenic function of the FDG1 and HMGB2 genes. The FDG1 gene is the susceptible gene for the Aarskog–Scott's faciogenital dysplasia syndrome (Shalev et al. 2006) and the HMGB2 gene is a DNA-binding protein with pleiotropic biological functions (Yamada & Maruyama 2007). A previous study in fact showed that expression of the FDG1 gene could cause cell transformation (Whitehead et al. 1998). "
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    • "Recently, other studies have indicated a degree of variable expressivity, with mutations associated with ADHD and dysmorphic features [Orrico et al., 2005] and clinical variability in cognitive function [Shalev et al., 2006]. In addition, Lebel et al. [2002] reported a family with non-syndromic X-linked mental retardation and a missense mutation in FGD1. "
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