CANT1 mutation is also responsible for Desbuquois dysplasia, type 2 and Kim variant.

Background Desbuquois dysplasia (DD) is a recessively inherited condition characterised by short stature, generalised skeletal dysplasia and advanced bone maturation. DD is both clinically and radiographically heterogeneous, and two subtypes have been distinguished based on the presence (type 1) or absence (type 2) of an accessory metacarpal bone. In addition, an apparently distinct variant without additional metacarpal bone but with short metacarpals and long phalanges (Kim variant) has been described recently. Mutations in the gene that encodes for CANT1 (calcium-activated nucleotidase 1) have been identified in a subset of patients with DD type 1. Methods A series of 11 subjects with DD from eight families (one type 1, two type 2, five Kim variant) were examined for CANT1 mutations by direct sequencing of all coding exons and their flanking introns. Results Eight distinct mutations were identified in seven families (one type 1, one type 2 and all 5 Kim variant): three were nonsense and five were missense. All missense mutations occurred at highly conserved amino acids in the nucleotidase conserved regions of CANT1. Measurement of nucleotidase activity in vitro showed that the missense mutations were all associated with loss-of-function. Conclusion The clinical-radiographic spectrum produced by CANT1 mutations must be extended to include DD type 2 and Kim variant. While presence or absence of an additional metacarpal ossification centre has been used to distinguish subtypes of DD, this sign is not a distinctive criterion to predict the molecular basis in DD

CTXΦ-independent production of the RS1 satellite phage by Vibrio cholerae

The cholera toxin genes of Vibrio cholerae are encoded by the filamentous phage, CTXΦ. Chromosomal CTXΦ prophage DNA is often found flanked by copies of a related genetic element designated RS1, and RS1 DNA can be packaged into filamentous phage particles (designated RS1Φ) by using the CTXΦ morphogenesis genes. RS1Φ is a satellite phage that further controls expression and dissemination of CTXΦ. Here we describe a CTXΦ-independent mechanism for production of RS1Φ. A nontoxigenic environmental V. cholerae strain (55V71) was identified that supports production of RS1Φ. However, newly infected CTX-negative strains did not produce RS1Φ, indicating that additional 55V71 genes were involved in production of RS1Φ. Analysis of nucleic acids from phage preparations of 55V71 revealed a 7.5-kb single-stranded DNA, whose corresponding replicative form was found in plasmid preparations. This DNA likely corresponds to the genome of a new filamentous phage, which we have designated KSF-1Φ. The replicative form DNA of KSF-1Φ was cloned into pUC18, and the resulting construct pKSF-1.1 supported the production of RS1Φ particles by CTX-negative V. cholerae strains. RS1Φ particles produced in this way infect recipient V. cholerae strains by a mechanism that is independent of the CTXΦ receptor, the toxin-coregulated pilus. Thus, KSF-1Φ is capable of facilitating the transfer of the RS1 element to strains that do not express toxin coregulated pilus. Given that RS1Φ can enhance coproduction of CTXΦ particles, KSF-1Φ-mediated dissemination of RS1 may indirectly promote the spread of toxin genes among V. cholerae strains. This study also shows that filamentous phages can package diverse DNA elements and thus may play a role in horizontal transfer of more genes than previously appreciated