ABSTRACT
The use of collaborative exercises (CE) and proficiency tests (PT) as part of the governance programme for any forensic science laboratory has become commonplace and recommended by several international organisations. Traditionally these have been discipline-specific exercises testing a laboratory's ability in a single area of forensic science. However, the "real" world is normally more complex and, in many instances, forensic material must be examined for a number of different evidence types. This article summarises the concepts, planning, design, preparation, implementation, co-ordination and evaluation of the 2022 Multidisciplinary Collaborative Exercise (2022-MdCE) covering a range of forensic disciplines, specifically DNA, fingerprint, documents and handwriting. The exercise consisted of a questioned letter with typescript text and a signature. In addition, the letter contained a visible bloody fingermark in the area of the signature, a visible staining in the lower left-hand corner, a latent fingermark and an indented impression. The analysis of the results showed that, in the investigation of the bloody fingermark, the priority was given to the DNA examination. Some critical issues emerged in relation to the biological (DNA)/ink sampling strategies when applied before fingermark visualisation. Another outcome of the exercise has been to demonstrate the importance of indented impressions, which have been underestimated by a significant number of participants. As setters, more in-depth studies are needed to produce consistent samples. This concerns all the disciplined involved but especially DNA and fingermarks. Based on this exercise, it is believed that this approach to testing of forensic disciplines allows the analysis of good practice within the various scientific areas, as well as scrutinising the process and sequence of events for examining the material within a forensic laboratory in the best conservative way for all kind of evidences.
ABSTRACT
Blomstrand osteochondrodysplasia (BOCD) is a rare lethal skeletal dysplasia characterized by accelerated endochondral and intramembranous ossification. Comparison of the characteristics of BOCD with type I PTH/PTH-related peptide (PTHrP) receptor-ablated mice reveals striking similarities that are most prominent in the growth plate. In both cases, the growth plate is reduced in size due to a strongly diminished zone of resting cartilage and the near absence of columnar arrangement of proliferating chondrocytes. This overall similarity suggested that an inactivating mutation of the PTH/PTHrP receptor might be the underlying genetic defect causing BOCD. Indeed, inactivating mutations of the PTH/PTHrP receptor have been recently identified in two cases of BOCD. We describe here a novel inactivating mutation in the PTH/PTHrP receptor. Sequence analysis of all coding exons of the type I PTH/ PTHrP receptor gene and complementary DNA of a case with BOCD identified a homozygous point mutation in exon EL2 in which one nucleotide (G at position 1122) was absent. The mutation was inherited from both parents, supporting the autosomal recessive nature of the disease. The missense mutation resulted in a shift in the open reading frame, leading to a truncated protein that completely diverged from the wild-type sequence after amino acid 364. The mutant receptor, therefore, lacked transmembrane domains 5, 6, and 7; the connecting intra- and extracellular loops; and the cytoplasmic tail. Functional analysis of the mutant receptor in COS-7 cells and of dermal fibroblasts obtained from the case proved that the mutation was indeed inactivating. Neither the transiently transfected COS-7 cells nor the dermal fibroblasts responded to a challenge with PTH or PTHrP with a rise in intracellular cAMP levels, in sharp contrast to control cells. Our results provide further evidence that BOCD is caused by inactivating mutations of the type I PTH/PTHrP receptor and underscore the importance of this receptor in mammalian skeletal development.
