We present a 5-year-old female with a distinctive phenotype comprising global developmental delays, pre-and post-natal growth restriction, striking joint laxity with soft skin, and scoliosis. She had a triangular facies, a prominent forehead, proptosis, a small nose, and a small jaw. Her ocular findings included corneal clouding, colobomas of the iris and optic nerve, and posterior subcapsular cataracts. Exome sequencing identified homozygosity for c.970T>A, predicting p.(Cys324Ser), in the xylosylprotein 4-beta-galactosyltransferase, polypeptide 7 (B4GALT7) gene. Variant segregation was consistent with autosomal recessive inheritance and the missense substitution was predicted to be pathogenic. As the phenotype of this child is consistent with that described in other "linkeropathy" syndromes, we conclude that p.(Cys324Ser) is likely to be disease-causing. The eye features were a notable part of this child's presentation and mutations in the linkeropathy genes (XYLT1, XYLT2, B4GALT7, B3GALT6, and B3GAT3) can be associated with ocular findings, including blue sclerae, refractive errors, corneal clouding, strabismus, nystagmus, cataracts, glaucoma, and retinal abnormalities, including retinal detachment. The corneal clouding and cataracts in this patient may thus have been caused by her B4GALT7 mutation, but the colobomas are a novel phenotypic finding. However, a different genetic etiology or a role for modifying genetic factors has not been excluded in the etiology of her colobomas.

Aims-In this study, we investigated whether short-term exercise, known to promote hippocampal BDNF expression, would also enhance activity in the Porsolt forced swim test (FST), a model for assessing antidepressant efficacy. We also wished to determine whether exercise combined with antidepressants would be more effective at modifying behavior in the FST than either intervention alone. In parallel with this, we also expected that these interventions would preserve post-stress levels of BDNF, and that antidepressants designed to selectively enhance noradrenergic or serotonergic neurotransmission (reboxetine or citalopram, respectively) would have differential effects on behavior and BDNF expression.Main methods-Male Sprague-Dawley rats were treated with exercise (voluntary wheel running), reboxetine, citalopram, or the combination of exercise and each antidepressant, for 1 week. At the end of this period, a subset of animals from each treatment group underwent the FST. Post-stress levels of hippocampal BDNF mRNA were then quantified via in situ hybridization.Key findings-Our results indicate that while both exercise and antidepressant treatment preserved post-stress levels of hippocampal BDNF mRNA, each intervention led to a unique behavioral profile in the FST. We found that antidepressant treatment increased swimming time in the FST, but that exercise decreased swimming time. While the combination of reboxetine-plus-exercise led to an increase in climbing and diving, citalopram-plus-exercise reduced these behaviors.Significance-It is possible that active behaviors during the FST, though specific to antidepressant medications, may not reflect increased hippocampal BDNF expression or other survival-associated benefits. KeywordsAntidepressant; Norephinephrine; Serotonin; Growth factor; Physical activity; In situ hybridization; Depression model; Brain-derived neurotrophic factor (BDNF); norepinephrine and serotonin reuptake inhibitor (NSRI); selective serotonin reuptake inhibitor (SSRI)

Based on personal experiences from the pediatric core clerkship of the third year of medical school, this reflexive writing piece highlights the positive impact that a preceptor had on my development as a physician-in-training. The piece draws attention to the emphasis that this preceptor places on cultivating constructive, supportive patient-doctor relationships and on pursuing a career path that is congruent with our inclinations and abilities.