Evidence of digenic inheritance in autoinflammation-associated genes

Familial Mediterranean fever (FMF) has traditionally been considered as a monogenic autosomal recessive disorder caused by mutations in the MEFV gene with highest incidence among Mediterranean populations. In a considerable number of patients with typical FMF, only one MEFV mutation was identified and the possibility that more than one autoinflammatory gene may be responsible for their disease was investigated. In the present study, an extensive search for possible mutations in three hereditary recurrent fever (HRF) genes was performed in 128 MEFV heterozygous Greek–Cypriots clinically diagnosed based on their phenotype with FMF-like disease from a previous study. Sequence analysis was performed for MVK, TNFRSF1A and NLRP3 genes which is also known to cause HRFs. In total, three patients were identified with heterozygous mutations and a second mutation in an autoinflammatory gene. Two patients carried a MEFV mutation and a NLRP3 mutation, and an additional third carried a MEFV mutation and a TNFRSF1A mutation. Patient 1 carried MEFV p.[Val726Ala] (NM_000243.2:c.2177T >C) and NLRP3 p.[Val198Met] (NM_001243133.1:c.592G >A) variants and patient 2 carried MEFV p.[Glu148Gln] (NM_000243.2:c.442G >C) variant which is of uncertain significance and NLRP3 p.[Arg176Trp] (NM_001243133.1:c.526C >T). Lastly, patient 3 was identified to carry MEFV p.[Met694Val] (NM_000243.2:c.2080A >G) and TNFRSF1A p.[Arg121Gln] (NM_001065.3:c.362G >A) variants. The results from this study indicate that screening of genes known to cause HRFs in patients already identified with a single MEFV mutation, can reveal quite rare but potentially causative mutational combinations at different loci. Such interaction provide further evidence for possible locus–locus interactions and phenotypes resulting from digenic inheritance.     

Isospora atrata N. Sp. (Apicomplexa, Eimeriidae): a New Coccidium Isolated from Carduelis atrata (Passeriformes, Fringillidae)

ABSTRACT Large numbers of coccidian oocysts belonging to the genus Isospora were obtained from the intestinal contents of 98 Carduelis atrata imported into Italy from South America during the months of August through December 1994. The oocysts are sub-spherical and average 21 × 20.3 μm (19.4–23.5 μm × 18.5–22 μm), have a bilayered wall, and an oval polar granule (rarely two). The sporocysts are elliptical and measure 18.8 μm × 10.3 μm (17.5–18.94 μm × 9.5–11.0 μm). The Stieda body protrudes slightly from the end of the sporocyst. A large sporocyst residuum is present, consisting of many granules that may be in a compact mass or scattered. Since this Isospora sp.does not resemble any other species of Isospora previously described from birds of the genus Carduelis , it has been named Isospora atrata n. sp. after the host. Disseminated asexual stages were found in mononuclear cells derived from formalin-fixed post mortem material, suggesting this coccidian may represent an Atoxoplasma -like parasite. Four coccidia-free Serinus canarius L. cohabitated for a long period (4 mo) with infected C. atrata but oocysts were never found in the stool of these birds.     

Colonization of the Aeolian Islands by Pimelia rugulosa rugulosa Germar, 1824 (Coleoptera: Tenebrionidae) inferred from the genetic structure of populations: geological and environmental relations

The darkling beetle Pimelia rugulosa rugulosa Germar, 1824 was selected to investigate the process of colonization in a volcanic archipelago and the role of volcanism in determining spatial patterns of genetic variability. Analyses were conducted in the Aeolian Islands, located in the central Mediterranean directly off the Sicilian coast. Genetic variability and geographic structure were studied in individuals from each island of the archipelago based on sequences of the cytochrome c oxidase subunit 2 mitochondrial gene; a network approach was employed to identify haplotype lineages. A strong genetic structure, with no haplotype sharing among islands, was observed. Six separate lineages were identified that independently colonized different islands of the archipelago from the mainland and differentiated locally to form small haplogroups. Variability of observed haplogroups is correlated with island age and a positive correlation between tenebrionid diversity and mitotype diversity is reported. Some, yet undescribed, catastrophic event is hypothesized to explain the depletion of a substantial part of the genetic, as well as biological diversity in the island of Filicudi. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 104 , 29–37.