Ten novel FBN2 mutations in congenital contractural arachnodactyly:Delineation of the molecular pathogenesis and clinical phenotype

Congenital contractural arachnodactyly (CCA) is an autosomal dominant condition that shares skeletal features with Marfan syndrome (MFS), but does not have the ocular and cardiovascular complications that characterize MFS. CCA and MFS result from mutations in highly similar genes, FBN2 and FBN1, respectively. All the identified CCA mutations in FBN2 cluster in a limited region similar to where severe MFS mutations cluster in FBN1, specifically between exons 23 and 34. We screened exons 22 through 36 of FBN2 for mutations in 13 patients with classic CCA by single stranded conformational polymorphism analysis (SSCP) and then by direct sequencing. We successfully identified 10 novel mutations in this critical region of FBN2 in these patients, indicating a mutation detection rate of 75% in this limited region. Interestingly, none of these identified FBN2 mutations alter amino acids in the calcium binding consensus sequence in the EGF-like domains, whereas many of the FBN1 mutations alter the consensus sequence. Furthermore, analysis of the clinical data of the CCA patients with characterized FBN2 mutation indicate that CCA patients have aortic root dilatation and the vast majority lack evidence of congenital heart disease. These studies have implications for our understanding of the molecular basis of CCA, along with the diagnosis and genetic counseling of CCA patients. Hum Mutat 19:39-48, 2002. (C) 2001 Wiley-Liss, Inc

Ten novel FBN2 mutations in congenital contractural arachnodactyly: Delineation of the molecular pathogenesis and clinical phenotype

Congenital contractural arachnodactyly (CCA) is an autosomal dominant condition that shares skeletal features with Marfan syndrome (MFS), but does not have the ocular and cardiovascular complications that characterize MFS. CCA and MFS result from mutations in highly similar genes, FBN2 and FBN1, respectively. All the identified CCA mutations in FBN2 cluster in a limited region similar to where severe MFS mutations cluster in FBN1, specifically between exons 23 and 34. We screened exons 22 through 36 of FBN2 for mutations in 13 patients with classic CCA by single stranded conformational polymorphism analysis (SSCP) and then by direct sequencing. We successfully identified 10 novel mutations in this critical region of FBN2 in these patients, indicating a mutation detection rate of 75% in this limited region. Interestingly, none of these identified FBN2 mutations alter amino acids in the calcium binding consensus sequence in the EGF-like domains, whereas many of the FBN1 mutations alter the consensus sequence. Furthermore, analysis of the clinical data of the CCA patients with characterized FBN2 mutation indicate that CCA patients have aortic root dilatation and the vast majority lack evidence of congenital heart disease. These studies have implications for our understanding of the molecular basis of CCA, along with the diagnosis and genetic counseling of CCA patients. Hum Mutat 19:39-48, 2002. (C) 2001 Wiley-Liss, Inc

Prediction beyond the borders: ERP indices of boundary extension-related error

Boundary extension (BE) is a rapidly occurring memory error in which participants incorrectly remember having seen beyond the boundaries of a view. However, behavioral data has provided no insight into how quickly after the onset of a test picture the effect is detected. To determine the time course of BE from neural responses we conducted a BE experiment while recording EEG. We exploited a diagnostic response asymmetry to mismatched views (a closer and wider view of the same scene) in which the same pair of views is rated as more similar when the closer item is shown first than vice versa. On each trial, a closer or wider view was presented for 250 ms followed by a 250-ms mask and either the identical view or a mismatched view. Boundary ratings replicated the typical asymmetry. We found a similar asymmetry in ERP responses in the 265-285 ms interval where the second member of the close-then-wide pairs evoked less negative responses at left parieto-temporal sites compared to the wide-then-close condition. We also found diagnostic ERP effects in the 500-560 ms range, where ERPs to wide-then-close pairs were more positive at centro-parietal sites than in the other three conditions, which is thought to be related to participants’ confidence in their perceptual decision. The ERP effect in the 265-285 ms range suggests the falsely remembered region beyond the view-boundaries of S1 is rapidly available and impacts assessment of the test picture within the first 265 ms of viewing, suggesting that extrapolated scene structure may be computed rapidly enough to play a role in the integration of successive views during visual scanning