Early‐onset coenzyme Q10 deficiency associated with ataxia and respiratory chain dysfunction due to novel pathogenic COQ8A variants, including a large intragenic deletion

Coenzyme Q10 (CoQ10) deficiency is a clinically and genetically heterogeneous subtype of mitochondrial disease. We report two girls with ataxia and mitochondrial respiratory chain deficiency who were shown to have primary CoQ10 deficiency. Muscle histochemistry displayed signs of mitochondrial dysfunction—ragged red fibers, mitochondrial paracrystalline inclusions, and lipid deposits while biochemical analyses revealed complex II+III respiratory chain deficiencies. MRI brain demonstrated cerebral and cerebellar atrophy. Targeted molecular analysis identified a homozygous c.1015G>A, p.(Ala339Thr) COQ8A variant in subject 1, while subject 2 was found to harbor a single heterozygous c.1029_1030delinsCA variant predicting a p.Gln343_Val344delinsHisMet amino acid substitution. Subsequent investigations identified a large‐scale COQ8A deletion in trans to the c.1029_1030delinsCA allele. A skin biopsy facilitated cDNA studies that confirmed exon skipping in the fibroblast derived COQ8A mRNA transcript. This report expands the molecular genetic spectrum associated with COQ8A ‐related mitochondrial disease and highlights the importance of thorough investigation of candidate pathogenic variants to establish phase. Rapid diagnosis is of the utmost importance as patients may benefit from therapeutic CoQ10 supplementation

Novel roles of the chemorepellent axon guidance molecule RGMa in cell migration and adhesion

The repulsive guidance molecule A (RGMa) is a contact-mediated axon guidance molecule that has significant roles in central nervous system (CNS) development. Here we have examined whether RGMa has novel roles in cell migration and cell adhesion outside the nervous system. RGMa was found to stimulate cell migration from Xenopus animal cap explants in a neogenin-dependent and BMP-independent manner. RGMa also stimulated the adhesion of Xenopus animal cap cells, and this adhesion was dependent on neogenin and independent of calcium. To begin to functionally characterize the role of specific domains in RGMa, we assessed the migratory and adhesive activities of deletion mutants. RGMa lacking the partial von Willebrand factor type D (vWF) domain preferentially perturbed cell adhesion, while mutants lacking the RGD motif affected cell migration. We also revealed that manipulating the levels of RGMa in vivo caused major migration defects during Xenopus gastrulation. We have revealed here novel roles of RGMa in cell migration and adhesion and demonstrated that perturbations to the homeostasis of RGMa expression can severely disrupt major morphogenetic events. These results have implications for understanding the role of RGMa in both health and disease

Identification of molecular signatures specific for distinct cranial sensory ganglia in the developing chick

Background The cranial sensory ganglia represent populations of neurons with distinct functions, or sensory modalities. The production of individual ganglia from distinct neurogenic placodes with different developmental pathways provides a powerful model to investigate the acquisition of specific sensory modalities. To date there is a limited range of gene markers available to examine the molecular pathways underlying this process. Results Transcriptional profiles were generated for populations of differentiated neurons purified from distinct cranial sensory ganglia using microdissection in embryonic chicken followed by FAC-sorting and RNAseq. Whole transcriptome analysis confirmed the division into somato- versus viscerosensory neurons, with additional evidence for subdivision of the somatic class into general and special somatosensory neurons. Cross-comparison of distinct ganglia transcriptomes identified a total of 134 markers, 113 of which are novel, which can be used to distinguish trigeminal, vestibulo-acoustic and epibranchial neuronal populations. In situ hybridisation analysis provided validation for 20/26 tested markers, and showed related expression in the target region of the hindbrain in many cases. Results One hundred thirty-four high-confidence markers have been identified for placode-derived cranial sensory ganglia which can now be used to address the acquisition of specific cranial sensory modalities.</p

AFOMP Policy No 5: career progression for clinical medical physicists in AFOMP countries

This policy statement, which is the fifth of aseries of documents being prepared by the Asia-OceaniaFederation of Organizations for Medical Physics ProfessionalDevelopment Committee, gives guidance on howclinical medical physicists’ careers should progress fromtheir initial training to career end. It is not intended to beprescriptive as in some AFOMP countries career structuresare already essentially defined by employment awards andbecause such matters will vary considerably from countryto country depending on local culture, employment practicesand legislation. It is intended to be advisory and setout options for member countries and employers of clinicalmedical physicists to develop suitable career structures

AFOMP Policy Statement No. 4: Recommendations for continuing professional development systems for medical physicists in AFOMP countries

This policy statement, which is the fourth of a series of documents being prepared by the Asia-Oceania Federation of Organizations for Medical Physics Committees Professional Development Committee, gives guidance on how member countries could develop a continuing professional development system for ensuring that its clinical medical physicists are up-to-date in their knowledge and practice. It is not intended to be prescriptive as there are already several CPD systems successfully operated by AFOMP member countries and elsewhere that vary considerably in scope and structure according to local culture, practice and legislation but all of which are capable of ensuring that physicists are up-to-date. It is intended to be advisory and set out options for member countries to develop their individual CPD systems

AFOMP Policy Statement No. 3: recommendations for the education and training of medical physicists in AFOMP countries

AFOMP recognizes that clinical medical physicists should demonstrate that they are competent to practice their profession by obtaining appropriate education, training and supervised experience in the specialties of medical physics in which they practice, as well as having a basic knowledge of other specialties. To help its member countries to achieve this, AFOMP has developed this policy to provide guidance when developing medical physicist education and training programs. The policy is compatible with the standards being promoted by the International Organization for Medical Physics and the International Medical Physics Certification Board