J. Med. Genet.

Background: Primary microcephaly (MCPH) is a genetically heterogeneous disorder showing an autosomal recessive mode of inheritance. Affected individuals present with head circumferences more than three SDs below the age- and sex-matched population mean, associated with mild to severe mental retardation. Five genes (MCPH1, CDK5RAP2, ASPM, CENPJ, STIL) and two genomic loci, MCPH2 and MCPH4, have been identified so far. Methods and results: In this study, we investigated all seven MCPH loci in patients with primary microcephaly from 112 Consanguineous Iranian families. In addition to a thorough clinical characterisation, karyotype analyses were performed for all patients. For Homozygosity mapping, microsatellite markers were selected for each locus and used for genotyping. Our investigation enabled us to detect homozygosity at MCPH1 (Microcephalin) in eight families, at MCPH5 (ASPM) in thirtheen families. Three families showed homozygosity at MCPH2 and five at MCPH6 (CENPJ), and two families were linked to MCPH7 (STIL). The remaining 81 families were not linked to any of the seven known loci. Subsequent sequencing revealed eight, 10 and one novel mutations in Microcephalin, ASPM and CENPJ, respectively. In some families, additional features such as short stature, seizures or congenital hearing loss were observed in the microcephalic patient, which widens the spectrum of clinical manifestations of mutations in known microcephaly genes. Conclusion: Our results show that the molecular basis of microcephaly is heterogeneous; thus, the Iranian population may provide a unique source for the identification of further genes underlying this disorder

Genetics of intellectual disability in consanguineous families

Autosomal recessive (AR) gene defects are the leading genetic cause of intellectual disability (ID) in countries with frequent parental consanguinity, which account for about 1/7th of the world population. Yet, compared to autosomal dominant de novo mutations, which are the predominant cause of ID in Western countries, the identification of AR-ID genes has lagged behind. Here, we report on whole exome and whole genome sequencing in 404 consanguineous predominantly Iranian families with two or more affected offspring. In 219 of these, we found likely causative variants, involving 77 known and 77 novel AR-ID (candidate) genes, 21 X-linked genes, as well as 9 genes previously implicated in diseases other than ID. This study, the largest of its kind published to date, illustrates that high-throughput DNA sequencing in consanguineous families is a superior strategy for elucidating the thousands of hitherto unknown gene defects underlying AR-ID, and it sheds light on their prevalence

Fuel Processing for Solid Oxide Fuel Cells

Fuel flexibility is a major advantage of SOFC technology. In addition to H2, operations with synthesis gas, biogas, alcohols, and light hydrocarbons are feasible provided that appropriate conditions are respected. The chapter reviews the operational modes and the anodic materials that have been proposed in the literature to run SOFCs with non-H2 fuels, as well as the methods that can be applied to clean the fuel feedstock from impurities (tars and species based on sulfur, nitrogen, and halogen). SOFC stacks can be run under four main configurations, depending on the position of the reformer (external or integrated) and on the possibility of directly processing the incoming fuel in the anodic electrode (Sect. 4.3). The feasibility of direct reforming or oxidation operations needs to be evaluated based on thermodynamic (Sect. 4.4) and kinetic considerations (Sect. 4.5), in order to avoid impairing the anode due to carbon formation or poisoning with impurities. Although they are still the most widespread choice, the behavior of standard Ni-YSZ cermet anodes (Sect. 4.6) poses problems in terms of sulfur and C tolerance, especially when the steam supply is lowered to achieve direct oxidation modes. Several strategies can be adopted to overcome these issues, by modification of the anodic materials (Sect. 4.7): Ni can be partially substituted or alloyed with transition or noble metals; Ni can be entirely replaced by different metals or oxides; protective barriers or oxide ion transferring or storing materials (MIEC, OSM) can be added to the standard Ni-YSZ cermet. In the case of external reforming solutions, the catalyst also experiences coking and poisoning issues, and its lifetime can be improved by strategies similar to those applied in SOFC anodes (Sect. 4.8). Several methods are available to remove impurities from feedstock: Those based on the use of alkaline sorbents and on catalytic decomposition are reviewed (Sect. 4.9)