The face recognition deficit in prosopagnosia ('face-blindness') has been linked to a lack of holistic processing and the reliance on compensatory featural processing. Here, we emphasise temporal aspects and propose that prosopagnosics' performance depends critically on sufficient stimulus presentation times. In three face recognition experiments we investigated performance differences between thirteen subjects with congenital prosopagnosia and twenty-two age-matched controls. First, we compared reaction times under unlimited viewing and presentation times required for 80% accuracy in an old/new recognition task. Reaction and presentation times were correlated across individuals, and both were longer for prosopagnosics. In the second and third experiments, we tested recognition performance for limited presentation times (50 to 750 ms) either during the learning or the testing phase. In both experiments …

The apparent selectivity of agnosia for faces is termed prosopagnosia or face blindness. This cognitive dysfunction can be seen after traumatic events--involving at least the right occipital temporal region--or very frequently congenital in the absence of any detectable lesions. The familiarity of congenital prosopagnosia was studied in two independently ascertained collections of subjects with prosopagnosia. One was an unselected group of pupils and students who underwent a questionnaire based screening. The others were self reported subjects after having heard for the first time about the phenomenon of prosopagnosia from mass media citing our studies and/or from our homepage (www.prosopagnosia.de). Those who agreed with consecutive studies of their family members had mostly one or more prosopagnosic first degree relatives. The segregation patterns derived from 39 families are compatible with autosomal dominant inheritance. Hence, mutation(s) in one gene are sufficient for manifestation of the phenotype. Still fitting the concept of autosomal dominant inheritance, we have evidence for a slightly reduced penetrance (4 normal transmitters from distinct families) and one or two de novo mutations.

A total of 226 index cases from high-risk hereditary breast and ovarian cancer families of German origin who had tested negative for small nucleotide alterations in BRCA1 and BRCA2 were analyzed for gross genomic rearrangements at the two gene loci by the multiplex ligation-dependent probe amplification technique. Six large genomic alterations were identified in BRCA1, while no gross rearrangements were found in BRCA2. The six BRCA1 mutations included two novel mutations including a deletion of exon 5, and a deletion comprising exons 5-7, as well as three distinct gross alterations previously reported, including a deletion of exons 1A, 1B, and 2, two duplications of exon 13, and a deletion of exon 17. To understand the mechanisms underlying the genomic rearrangements within the BRCA1 gene and to provide a simple PCR-based assay for further diagnostic applications, we have defined the molecular breakpoints of the deletion/insertion mutations. In all cases, our data point to a mechanism by which illegitimate crossing over between stretches of direct repeat sequences as small as 9 base pairs (bp) and up to 188 bp may have occurred. Overall, we provide evidence that gross rearrangements within the BRCA1 gene locus may be as frequent as 3% in primarily mutation-negative tested high-risk familial breast and ovarian cancer of German ancestry, while large alterations involving the BRCA2 locus do not appear to play a significant role in disease etiology. These findings have important implications for genetic counseling and testing of high-risk breast and ovarian cancer families.

The 13 polypeptides encoded in mitochondrial DNA (mtDNA) are synthesized in the mitochondrial matrix on a dedicated protein-translation apparatus that resembles that found in prokaryotes. Here, we have investigated the genetic basis for a mitochondrial protein-synthesis defect associated with a combined oxidative phosphorylation enzyme deficiency in two patients, one of whom presented with encephalomyopathy and the other with hypertrophic cardiomyopathy. Sequencing of candidate genes revealed the same homozygous mutation (C997T) in both patients in TSFM, a gene coding for the mitochondrial translation elongation factor EFTs. EFTs functions as a guanine nucleotide exchange factor for EFTu, another translation elongation factor that brings aminoacylated transfer RNAs to the ribosomal A site as a ternary complex with guanosine triphosphate. The mutation predicts an Arg333Trp substitution at an evolutionarily conserved site in a subdomain of EFTs that interacts with EFTu. Molecular modeling showed that the substitution disrupts local subdomain structure and the dimerization interface. The steady-state levels of EFTs and EFTu in patient fibroblasts were reduced by 75% and 60%, respectively, and the amounts of assembled complexes I, IV, and V were reduced by 35%-91% compared with the amounts in controls. These phenotypes and the translation defect were rescued by retroviral expression of either EFTs or EFTu. These data clearly establish mutant EFTs as the cause of disease in these patients. The fact that the same mutation is associated with distinct clinical phenotypes suggests the presence of genetic modifiers of the mitochondrial translation apparatus.

Acquired prosopagnosia (PA) is a rare condition after, for example, a stroke or brain injury. The congenital form of PA is generally considered to be even less common. Beside a few single case reports and anecdotal mentioning of familial cases no data on the epidemiology exists. Following a questionnaire-based screening in local secondary schools and at our medical faculty, candidates suspicious for PA underwent a semi-structured interview followed by examinations of first degree relatives. Among 689 local pupils and medical students of our university we found 17 with congenital PA. This corresponds to a prevalence rate of 2.47% (95% CI 1.31-3.63). The frequency is among the highest known for a monogenic disorder. All those index subjects (n = 14) of the target group who agreed to further examinations of their family members had other first degree relatives with the same cognitive disorder. This study provides epidemiological evidence that congenital PA is a very common cognitive disorder which almost always runs in families. The segregation pattern of this hereditary prosopagnosia (HPA) is fully compatible with autosomal dominant inheritance.

Ziele: Wie hoch ist die detektierte Mammakarzinomrate in einem humangenetisch definierten Risikokollektiv in einer 1. Screeningrunde, die Mammographie, Ultraschall und MR-Mammographie (MRM) umfasst? Methode: Als Teil einer von der Deutschen Krebshilfe unterstützten Multicenterstudie wurden in Münster von 12/02–10/03 90 Frauen (30–69 Jahre) eingeschlossen, die nach den Chang-Claude-Tabellen oder nach statistischer Berechnung mit dem Computerprogramm „Cyrillic 2.1“ ein medianes Risiko von 35% zugewiesen bekamen. In diesem Kollektiv lagen bei n=9 Patientinnen eine positive BRCA1-Testung, bei n=3 eine positive BRCA2-Testung und bei n=13 nachgewiesene BRCA1/2-Varianten (UV) vor. Dem jährlichen Intervall der Mammographie angepaßt, wurden am gleichen Tag eine Mammographie, eine Ultraschalluntersuchung (7,5MHz) und eine MRM (1,5T) zunächst separat durchgeführt und dann synoptisch befundet. Ergebnis: 5 T1-Karzinome bei 3 Frauen (Alter 39–63 Jahre, Risiko: 20% (BRCA-UV); 16% (keine Testung); 70% (BRCA2) wurden richtig positiv diagnostiziert. In der MRM wurden 5/5 Karzinome detektiert, mit dem Ultraschall 3/5 und mit der Mammographie 1/5. Zusätzlich wurden histologisch 1 richtig negativer Befund (progredientes Fibroadenom) und 2 falsch negative Befunde (Fibroadenom, Skleradenose) aufgrund der MRM- bzw. Mammographiebefundung gesichert. Schlussfolgerung: Die detektierte Karzinomrate ohne mögliche ausstehende falsch negativ bestätigte Befunde aus der künftigen 2. Screeningrunde übersteigt in dem humangenetisch rekrutierten Kollektiv die zu erwartende sporadische Rate. Die MRM ermöglicht im Vergleich zur Mammographie und zum Ultraschall die beste Detektionsrate.