Genetic variant of TTLL11 gene and subsequent ciliary defects are associated with idiopathic scoliosis in a 5-generation UK family

Idiopathic scoliosis (IS) is a complex 3D deformation of the spine with a strong genetic component, most commonly found in adolescent girls. Adolescent idiopathic scoliosis (AIS) affects around 3% of the general population. In a 5-generation UK family, linkage analysis identified the locus 9q31.2-q34.2 as a candidate region for AIS; however, the causative gene remained unidentified. Here, using exome sequencing we identified a rare insertion c.1569_1570insTT in the tubulin tyrosine ligase like gene, member 11 (TTLL11) within that locus, as the IS causative gene in this British family. Two other TTLL11 mutations were also identified in two additional AIS cases in the same cohort. Analyses of primary cells of individuals carrying the c.1569_1570insTT (NM_194252) mutation reveal a defect at the primary cilia level, which is less present, smaller and less polyglutamylated compared to control. Further, in a zebrafish, the knock down of ttll11, and the mutated ttll11 confirmed its role in spine development and ciliary function in the fish retina. These findings provide evidence that mutations in TTLL11, a ciliary gene, contribute to the pathogenesis of IS.

Two new species of Amanita sect. Phalloideae from Africa, one of which is devoid of amatoxins and phallotoxins

Two new species of Amanitasect.Phalloideae are described from tropical Africa (incl. Madagascar) based on both morphological and molecular (DNA sequence) data. Amanitabweyeyensissp. nov. was collected, associated with Eucalyptus, in Rwanda, Burundi and Tanzania. It is consumed by local people and chemical analyses showed the absence of amatoxins and phallotoxins in the basidiomata. Surprisingly, molecular analysis performed on the same specimens nevertheless demonstrated the presence of the gene sequence encoding for the phallotoxin phallacidin (PHA gene, member of the MSDIN family). The second species, Amanitaharkonenianasp. nov. was collected in Tanzania and Madagascar. It is also characterised by a complete PHA gene sequence and is suspected to be deadly poisonous. Both species clustered together in a well-supported terminal clade in multilocus phylogenetic inferences (including nuclear ribosomal partial LSU and ITS-5.8S, partial tef1-α, rpb2 and β-tubulin genes), considered either individually or concatenated. This, along with the occurrence of other species in sub-Saharan Africa and their phylogenetic relationships, are briefly discussed. Macro- and microscopic descriptions, as well as pictures and line drawings, are presented for both species. An identification key to the African and Madagascan species of Amanitasect.Phalloideae is provided. The differences between the two new species and the closest Phalloideae species are discussed.