Präimplantationsdiagnostik in der Schweiz: Möglichkeiten und Probleme

Die durch das revidierte Fortpflanzungsmedizingesetz in der Schweiz erlaubte Präimplantationsgenetik ermöglicht es einerseits, eine bessere reproduktionsmedizinische Behandlung anzubieten. Andererseits tun sich auch Problem Felder auf, was die praktische Umsetzung betrifft

Genetische Diagnostik für die Betreuung von Patientinnen mit Brustkrebs: BRCA and beyond

Diese kurze Übersicht zur hereditären Brustkrebserkrankung soll illustrieren, wie wichtig es ist, Patienten mit erhöhtem Erkrankungsrisiko zu identifizieren und den Betroffenen, falls gewünscht, eine genetische Testung anzubieten, um den Patienten und auch deren Verwandten die bestmögliche individuelle Betreuung zu bieten. Ein Schritt Richtung personalisierter Medizin

Entwicklung der genetischen und genomischen Medizin in der Schweiz

Mit den rasanten technologischen Entwicklungen im medizinisch-genomischen Bereich und dem damit verbundenen exponentiellen Kenntniszuwachs hat der Bedarf an genetischer Expertise in praktisch allen medizinischen Disziplinen zugenommen. Die Schweizerische Gesellschaft für Medizinische Genetik (SGMG) sieht sich als Fachgesellschaft und Vertreterin einer transversalen medizinischen Disziplin besonders geeignet, die gegebene Situation zu evaluieren und zukünftige Konzepte zu entwickeln und zu begleiten

Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly

Purpose: Microcephaly is a sign of many genetic conditions but has been rarely systematically evaluated. We therefore comprehensively studied the clinical and genetic landscape of an unselected cohort of patients with microcephaly. Methods: We performed clinical assessment, high-resolution chromosomal microarray analysis, exome sequencing, and functional studies in 62 patients (58% with primary microcephaly [PM], 27% with secondary microcephaly [SM], and 15% of unknown onset). Results: We found severity of developmental delay/intellectual disability correlating with severity of microcephaly in PM, but not SM. We detected causative variants in 48.4% of patients and found divergent inheritance and variant pattern for PM (mainly recessive and likely gene-disrupting [LGD]) versus SM (all dominant de novo and evenly LGD or missense). While centrosome-related pathways were solely identified in PM, transcriptional regulation was the most frequently affected pathway in both SM and PM. Unexpectedly, we found causative variants in different mitochondria-related genes accounting for ~5% of patients, which emphasizes their role even in syndromic PM. Additionally, we delineated novel candidate genes involved in centrosome-related pathway (SPAG5, TEDC1), Wnt signaling (VPS26A, ZNRF3), and RNA trafficking (DDX1). Conclusion: Our findings enable improved evaluation and genetic counseling of PM and SM patients and further elucidate microcephaly pathways

Hochdurchsatz-Sequenzierung

Die rasante technische Entwicklung in der medizinischen Genetik in den vergangenen Jahren hat dazu geführt, dass mit der Hochdurchsatz-Sequenzierung mehrere Gene, das gesamte Exom oder sogar das gesamte Exom gleihzeitig sequenziert werden können

Ohne X geht nix

Dank der Arbeit der Gruppen im Human Genom Projekt konnte in den letzten Jahren immer mehr der Sequenz des menschlichen Genoms entziffert werden. Daraus ergeben sich einerseits interessante Rückschlüsse auf die Evolution des Menschen, aber auch neue Möglichkeiten in der heutigen Diagnostik der medizinischen Genetik und für die Zukunft interessante Ansätze in der Therapie genetisch bedingter Erkrankungen. Neben der Genetik an sich wird in Fachkreisen die Epigenetik zu einem immer wichtigeren Begriff, wobei dazu noch lange nicht alle Fragen beantwortet werden können. Ganz wichtig aber ist und bleibt, dass der Mensch als Individuum, Teil seiner Familie und Gesellschaft bei all den technischen Fortschritten nicht vergessen geht

Survival with trisomy 18--data from Switzerland

We collected records of 352 cases of trisomy 18 karyotyped between 1964 and May 2003 from the two major cytogenetic laboratories in Northeastern Switzerland. For more detailed information about the cases we contacted the referring physicians and/or the families of the patients. In this way we collected data about survival and malformations of 161 live births, 136 induced abortions and 29 stillborns or spontaneous abortions. In 26 cases of trisomy 18, only incomplete records were available. We observed that each year more cases of trisomy 18 were cytogenetically diagnosed in the two laboratories. Before 1984 almost no prenatal diagnoses were made; however, after this date the number of prenatal diagnoses increased and in the last 10 years, accounted for 75% of all cases. A decrease in the number of postnatally diagnosed cases was also observed over the same period of time. One third of the live-born children with trisomy 18 died during the first day of life. After 1 week, 1 month and 1 year of life the survival rates were 40, 22 and 6%, respectively. The median survival was 4 days, and only 1% of the children survived until their 10th birthday. Females were more likely to survive long term. In 63 cases autopsy reports were available for review. In 97% of these cases three or more malformations were found: 67% had VSD, 32% had horseshoe kidneys, 21% had esophageal atresia, 14% had omphalocele, 14% had facial clefts, and 11% had diaphragmatic hernias. In more than 50% genital hypoplasia was also described. We further analyzed survival of live-borns in relation to the length of gestation and to VSD and esophageal atresia

Grundlagen der medizinischen Genetik

The human genome consists of 23 pairs of chromosomes that contain 20 000-25 000 genes. Genetic disorders can be caused by different mechanisms, and therefore the confirmation of a suspected diagnosis requires knowledge of the underlying defect, so that the correct test can be applied. Monogenic diseases are caused by disturbances in a single gene, and currently only targeted diagnostic testing is available following a specific clinical suspicion. Chromosomal disorders usually involve multiple genes, so that the symptoms are often less specific. Specialists in Medical Genetics FMH are trained in creating a clinical genetic differential diagnosis, requesting the according laboratory test, interpretating the results and providing expert genetic counseling in presymptomatic and prenatal diagnosis. In Switzerland, specific legal principles and ethical guidelines must be taken into account

An unexpected finding: younger fathers have a higher risk for offspring with chromosomal aneuploidies

The past decades have seen a remarkable shift in the demographics of childbearing in Western countries. The risk for offspring with chromosomal aneuploidies with advancing maternal age is well known, but most studies failed to demonstrate a paternal age effect. Retrospectively, we analyzed two case data sets containing parental ages from pre- and postnatal cases with trisomies 21, 13 and 18. The reference data set contains the parental ages of the general Swiss population. We dichotomized all couples into two distinct groups. In the first group, the mothers' integral age was as least as the father's age or older. We compared the frequency of cases in nine 5-year intervals of maternal age. In addition, we computed logistic regression models for the binary endpoint aneuploidy yes/no where paternal ages were incorporated as linear or quadratic, as well as smooth functions within a generalized additive model framework. We demonstrated that the proportion of younger fathers is uniformly different between cases and controls of live-born trisomy 21 as well, although not reaching significance, for fetuses over all mother's ages. Logistic regression models with different strategies to incorporate paternal ages confirmed our findings. The negative paternal age effect was also found in pre- and postnatal cases taken together with trisomies 13 and 18. The couples with younger fathers face almost twofold odds for a child with Down syndrome (DS). We estimated odds curves for parental ages. If confirmation of these findings can be achieved, the management of couples at risk needs a major correction of the risk stratification.European Journal of Human Genetics advance online publication, 9 July 2014; doi:10.1038/ejhg.2014.122