Bounding uncertainties around the conceptual representation of species in radiological assessment in the context of routine atmospheric release.

Wildlife protection has become of regulatory interest since the International Commission on Radiological Protection (ICRP) developed an approach to assess the level of radiological protection specifically for animals and plants. For the purpose of demonstrating compliance with regulation to protect the environment against routine authorised discharges from nuclear facilities, the wide variety of biota inhabiting an ecosystem needs to be condensed to a limited set of representative organisms, as proposed by the ICRP with a set of 'reference animals and plants' which can be considered representative of many other species. It is now recommended in the International Atomic Energy Agency Safety Standards, and internationally accepted, that the use of such a limited number of organisms to represent a pool of species is adequate for radiation protection purposes, particularly in planned exposure situations.

Overview of the MODARIA programme (and comments on implications for future programmes of work).

The International Atomic Energy Agency (IAEA) has organised programmes on the development, comparison and testing of environmental assessment models and approaches for estimating the radiation exposure of humans and wildlife since the 1980s. The latest of these programmes was called MODARIA (Modelling and Data for Radiological Impact Assessment) and was run in two phases from 2012 to 2015 (MODARIA I) and 2016 to 2019 (MODARIA II). Both phases of the MODARIA programme had the overall objective to improve capabilities in the field of environmental transfer of radionuclides and public and non-human biota exposures assessment, by means of acquisition of improved data for model testing and comparison, reaching consensus on modelling philosophies, approaches and parameter values and building an international forum for the exchange of information.

Co-occurrence of neurofibromatosis type 1 and optic nerve gliomas with autosomal dominant polycystic kidney disease type 2.

Background: Autosomal dominant polycystic kidney disease (ADPKD) and neurofibromatosis type 1 (NF1) are both autosomal dominant disorders with a high rate of novel mutations. However, the two disorders have distinct and well-delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and NF1 in a single individual have been reported, but the possible implications of this association are unknown.

Insights into the pathophysiology of DFNA10 hearing loss associated with novel EYA4 variants.

The mutational spectrum of many genes and their contribution to the global prevalence of hereditary hearing loss is still widely unknown. In this study, we have performed the mutational screening of EYA4 gene by DHLPC and NGS in a large cohort of 531 unrelated Spanish probands and one Australian family with autosomal dominant non-syndromic hearing loss (ADNSHL). In total, 9 novel EYA4 variants have been identified, 3 in the EYA4 variable region (c.

Does the use of reference organisms in radiological impact assessments provide adequate protection of all the species within an environment?

Non-human biota in radiological risk assessment is typically evaluated using Reference Organisms (ROs) or Reference Animals and Plants (RAPs), for all exposure situations. However, it still remains open whether the use of an increased number of species would improve the ability to demonstrate protectiveness of the environment. In this paper, the representativeness of a broader list of fauna is tested in terms of the geometrical characteristics and habits for radiological risk assessments in the case of routine discharges from a nuclear installation: the Cadarache centre.

Use of the ICRP system for the protection of marine ecosystems.

The International Commission on Radiological Protection (ICRP) recently reinforced the international system of radiological protection, initially focused on humans, by identifying principles of environmental protection and proposing a framework for assessing impacts of ionising radiation on non-human species, based on a reference flora and fauna approach. For this purpose, ICRP developed dosimetric models for a set of Reference Animals and Plants, which are representative of flora and fauna in different environments (terrestrial, freshwater, marine), and produced criteria based on information on radiation effects, with the aim of evaluating the level of potential or actual radiological impacts, and as an input for decision making. The approach developed by ICRP for flora and fauna is consistent with the approach used to protect humans.

The IAEA handbook on radionuclide transfer to wildlife.

An IAEA handbook presenting transfer parameter values for wildlife has recently been produced. Concentration ratios (CRwo-media) between the whole organism (fresh weight) and either soil (dry weight) or water were collated for a range of wildlife groups (classified taxonomically and by feeding strategy) in terrestrial, freshwater, marine and brackish generic ecosystems. The data have been compiled in an on line database, which will continue to be updated in the future providing the basis for subsequent revision of the Wildlife TRS values.

A highly sensitive genetic protocol to detect NF1 mutations.

Neurofibromatosis type 1 (NF1) is a hereditary disorder caused by mutations in the NF1 gene. Detecting mutation in NF1 is hindered by the gene's large size, the lack of mutation hotspots, the presence of pseudogenes, and the wide variety of possible lesions. We developed a method for detecting germline mutations by combining an original RNA-based cDNA-PCR mutation detection method and denaturing high-performance liquid chromatography (DHPLC) with multiplex ligation-dependent probe amplification (MLPA).

Genetic characterization and structural analysis of VHL Spanish families to define genotype-phenotype correlations.

Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. This gene, located in the 3p25-26 chromosome, is a tumor suppressor gene associated with the inhibition of angiogenesis and apoptosis, cell cycle exit, fibronectin matrix assembly, and proteolysis. To define the molecular basis of VHL in a Spanish population, we studied 33 patients suspected of suffering familial or de novo VHL disease and two familial pheochromocytoma cases.

Identification of novel SDHD mutations in patients with phaeochromocytoma and/or paraganglioma.

Familial paraganglioma is a dominantly inherited disorder characterised by the development of highly vascular tumours in the head and neck. Recently, a relationship between hereditary tumours derived from the autonomic nervous system and germline mutations in the gene encoding succinate dehydrogenase complex subunit D (SDHD) is increasingly a subject of study. Familial paraganglioma syndrome is embryologically related to phaeochromocytoma, another neuroendocrine tumour that shows great aetiological and genetic heterogeneity.

Insulin gene variable number of tandem repeats regulatory polymorphism is not associated with hyperandrogenism in Spanish women.

Objective: To determine if the insulin gene variable number of tandem repeats (VNTR) regulatory polymorphism is associated with hyperandrogenism in a population of Spanish women.

Design: Controlled clinical study.

Setting: Tertiary institutional hospital.

A deletion involving the connexin 30 gene in nonsyndromic hearing impairment.

Background: Inherited hearing impairment affects about 1 in 2000 newborns. Up to 50 percent of all patients with autosomal recessive nonsyndromic prelingual deafness in different populations have mutations in the gene encoding the gap-junction protein connexin 26 (GJB2) at locus DFNB1 on chromosome 13q12. However, a large fraction (10 to 42 percent) of patients with GJB2 mutations have only one mutant allele; the accompanying mutation has not been identified.

Screening for mutations in the steroidogenic acute regulatory protein and steroidogenic factor-1 genes, and in CYP11A and dosage-sensitive sex reversal-adrenal hypoplasia gene on the X chromosome, gene-1 (DAX-1), in hyperandrogenic hirsute women.

Abstract Abnormalities in adrenal and/or ovarian steroidogenesis are found in most patients with hirsutism. The rate-limiting step in the synthesis of steroids in the ovary and the adrenal is the conversion of cholesterol into pregnenolone by cholesterol side-chain cleavage enzyme (P450scc), encoded by the gene CYP11A, after cholesterol is introduced into the mitochondria by the steroidogenic acute regulatory protein (StAR). DAX-1 is a repressor of StAR gene expression, and steroidogenic factor-1 (SF-1) is a regulator of CYP11A, DAX-1, and StAR gene.

[Mutational analysis of the PKD1 and PKD2 (type 1 and 2 dominant autosomal polycystic kidney) genes].

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It is caused by mutations in at least two different genes: PKD1 and PKD2. The study of mutations in these genes is very difficult nowadays.

A novel frameshift mutation (2436insT) produces an immediate stop codon in the autosomal dominant polycystic kidney disease 2 (PKD2) gene.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder that can be caused by mutations in at least three different genes. Several mutations have been identified in PKD1 and PKD2 genes. Most of the mutations found in PKD2 gene are predicted to cause premature termination of the protein.

Seven novel mutations of the PKD2 gene in families with autosomal dominant polycystic kidney disease.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous, with at least three chromosomal loci accounting for the disease. Mutations in the PKD2 gene on the long arm of chromosome 4 are expected to be responsible for approximately 15% of cases of ADPKD.

Methods: We report a systematic screening for mutations covering the 15 exons of the PKD2 gene in eight unrelated families with ADPKD type 2, using the heteroduplex technique.

Novel stop and frameshifting mutations in the autosomal dominant polycystic kidney disease 2 (PKD2) gene.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequent inherited disorders. The majority of cases are due to mutation of the PKD1 gene, on 16p13.3, while in most of the remainder the disease maps to the PKD2 locus, at chromosome 4q21-q23.