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Adams-Oliver syndrome (AOS) is defined by the combination of limb abnormalities and scalp defects, often accompanied by skull ossification defects. We studied nine families affected with AOS, eight of which have not been clinically described before. In our patients, scalp abnormalities were most often found, followed by limb and skull defects. The most common limb abnormalities appeared to be brachydactyly, syndactyly of toes 2 and 3 and hypoplastic toenails. Additional features observed were cutis marmorata telangiectatica congenita, cryptorchidism and cardiac abnormalities. In an attempt to identify the diseasecausing mutations in our families, we selected two genes, ALX4 and MSX2, which were considered serious candidates based on their known function in skull and limb development. Mutation analysis of both genes, performed by direct sequencing, identified several polymorphisms, but no disease-causing mutations. Therefore, we can conclude that the AOS in our set of patients is not caused by mutations in ALX4 or MSX2.

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PurposePreimplantation genetic diagnosis (PGD) is a reproductive option for BRCA1/2 mutation carriers wishing to avoid transmission of the predisposition for hereditary breast and ovarian cancer (HBOC) to their offspring. Embryos obtained by in vitro fertilisation (IVF/ICSI) are tested for the presence of the mutation, only BRCA-negative embryos are transferred into the uterus. The suitability and outcome of PGD for HBOC is evaluated. MethodsObservational cohort study on PGD treatments for HBOC carried out in two of WesternEurope's largest PGD centres from 2006 until 2012. Male carriers, asymptomatic female carriers, and breast cancer survivors were eligible. If available, PGD on embryos cryopreserved before chemotherapy was possible. Generic PGD-PCR tests were developed based on haplotyping, if necessary combined with mutation detection. Results 70couples underwent PGD for BRCA1/2. 42/71 carriers (59.2%) were female, six (14.3%) of whom have had breast cancer prior to PGD. In total, 145 PGD cycles were performed. 720 embryos were tested, identifying 294 (40.8%) as BRCA-negative. Of fresh IVF/PGD cycles, 23.9% resulted in a clinical pregnancy. Three cycles involved PGD on embryos cryopreserved before chemotherapy; two of these women delivered a healthy child. Overall, 38 children were liveborn. Two BRCA1 carriers were diagnosed with breast cancer shortly after PGD treatment, despite negative screening prior to PGD. ConclusionsPGD for HBOC proved to be suitable, yielding good pregnancy rates for asymptomatic carriers as well as breast cancer survivors. Because of two cases of breast cancer shortly after treatment, maternal safety of IVF(/PGD) in female carriers needs further evaluation. [2,3]. The prevalence of germline BRCA1/2 mutations is estimated at 0.1-1.0% in the general population, making HBOC one of the more prevalent autosomal dominant genetic disorders [4,5].Carriers of a BRCA1/2 mutation have a 50% risk of passing this predisposition to their offspring. There are several reproductive options to circumvent this, but only two lead to a child genetically related to both partners: prenatal diagnosis and preimplantation genetic diagnosis (PGD). Prenatal diagnosis on the one hand, involves genetic testing of a fetus for the presence of a familial BRCA1/2 mutation during pregnancy, followed by pregnancy termination in case of an unfavourable result. Although applied on a small scale, reports regarding clinical experience with prenatal diagnosis for HBOC are not available in the literature to date. Preimplantation genetic diagnosis (PGD) on the other hand, involves in vitro fertilisation (IVF) with intracytoplasmic sperm injection (ICSI), followed by genetic testing of the embryos for the presence of a familial BRCA1/2 mutation before intrauterine transfer.PGD has been successfully applied since 1990 for an expanding list of monogenic disorders and chromosomal abnormalities [6]. In 2003, the Ethics Taskforce of the European Society of Human Reproduction and Embryology stated that it is acceptable to ...

Due to the pronounced morphological variation and geographical distribution of Galápagos' Opuntia cacti, numerous hypotheses have been advanced regarding their radiation, diversification, and classification. The currently accepted classification is based on morphology and recognizes six species and fourteen varieties, but the plasticity of many of the characteristics renders any morphological taxonomy problematic. Our analysis of previously published morphological data agrees only partially with the current classification. We present the first molecular phylogeny of these plants. Multiple DNA sequences indicate little genetic distinction among the currently identified species, despite restricted gene flow and limited long distance dispersal within the archipelago. No clear relationship exists between morphological and genetic differences. These results suggest that both molecular and morphological data should be used in conservation planning.