Autosomal dominant Weill-Marchesani-like syndrome in a Chinese family due to novel haplotypic mutations in LTBP2.

INTRODUCTION: Weill-Marchesani syndrome (WMS) is a hereditary connective tissue disorder with substantial heterogeneity in clinical features and genetic etiology, so it is essential to define the full mutation spectrum for earlier diagnosis. In this study, we report Weill-Marchesani-like syndrome (WMS-like) change to autosomal dominance inheritance caused by novel haplotypic mutations in latent transforming growth factor beta-binding protein 2 (LTBP2). METHODS: Twenty-five members from a 4-generation Chinese family were recruited from Guangzhou, of whom nine were diagnosed with WMS-like disease, nine were healthy, and seven were of "uncertain" clinical status because of their young age. All members received detailed physical and ocular examinations. Whole exome sequencing, Sanger sequencing, and real-time PCR were used to identify and verify the causative mutations in family members. RESULTS: Genetic sequencing revealed novel haplotypic mutations on the same LTBP2 chromosome associated with WMS-like, c. 2657C>A/p.T886K in exon 16 and deletion of exons 25-36. Real-time PCR and Sanger sequencing verified both mutations in patients with clinically diagnosed WMS-like, and in one "uncertain" child. In these patients, the haplotypic mutations led to ectopia lentis, short stature and obesity. CONCLUSION:  Our study revealed that WMS-like may be associated with haplotypic LTBP2 mutations with autosomal dominant inheritance.

Depression in multiple system atrophy: Views on pathological, clinical and imaging aspects.

Multiple system atrophy (MSA) is a common atypical parkinsonism, characterized by a varying combination of autonomic, cerebellar, and pyramidal systems. It has been noticed that the patients with MSA can be accompanied by some neuropsychiatric disorders, in particular depression. However, there is limited understanding of MSA-related depression. To bridge existing gaps, we summarized research progress on this topic and provided a new perspective regarding pathological, clinical, and imaging aspects. Firstly, we synthesized corresponding studies in order to investigate the relationship between depression and MSA from a pathological perspective. And then, from a clinical perspective, we focused on the prevalence of depression in MS patients and the comparison with other populations. Furthermore, the associations between depression and some clinical characteristics, such as life quality and gender, have been reported. The available neuroimaging studies were too sparse to draw conclusions about the radiological aspect of depression in MSA patients but we still described them in the presence of paper. Finally, we discussed some limitations and shortcomings existing in the included studies, which call for more high-quality basic research and clinical research in this field.

Sensorimotor Responses in Post-Stroke Hemiplegic Patients Modulated by Acupuncture at Yanglingquan (GB34): A fMRI Study Using Intersubject Functional Correlation (ISFC) Analysis.

Motor dysfunction is common in patients with stroke. Acupuncture has become an acceptable alternative method for stroke rehabilitation. Previous studies have shown various functional connectivity changes activated by acupuncture. We introduced intersubject correlation (ISC) and intersubject functional correlation (ISFC) analyses into the functional magnetic resonance imaging (fMRI) for ischemic stroke to seek a common activation and suppression pattern triggered by acupuncture. In this study, 63 ischemic stroke patients with motor dysfunction and 42 normal controls were analyzed. Three functional scans were conducted during the resting state, motor task, and acupuncture at Yanglingquan (GB34) task. Twenty-two sensory, motor, and movement-imagination cortices in the bilateral hemispheres were selected as the region of interest (ROI). We performed ISC and ISFC analyses among these ROIs in three fMRI runs on patients and controls. Subgroup analyses by course or severity were also conducted. The results showed that acupuncture at GB34 triggered ISFC among upper limb motor, upper limb/hand/face, lower limb, tongue/larynx sensory, and movement imagination regions in the patient group. Subgroup ISC and ISFC analyses showed that patients tended to have increasing responses in the early stage of stroke (within 1 month) and decreasing responses afterward (1-3 months). Patients with mild clinical functional damage (NIHSS 2-4) tended to generate more responses via acupuncture than those with moderate damage (NIHSS 5-15). Our findings may help understand the clinical effects and modulatory features of acupuncture based on the group-level post-stroke neuroplasticity.

Signatures of selection in recently domesticated macadamia.

Macadamia is a high value nut crop that is recently domesticated, ideal for testing the effect of artificial selection. Here, we sequence the genome of Hawaiian cultivar 'Kau' and assemble into 794 Mb in 14 pseudo-chromosomes with 37,728 genes. Genome analysis reveals a whole-genome duplication event, occurred 46.8 million years ago. Gene expansions occurred in gene families involves in fatty acid biosynthesis. Gene duplication of MADS-Box transcription factors in proanthocyanidin biosynthesis are relevant for seed coat development. Genome re-sequencing of 112 accessions reveals the origin of Hawaiian cultivars from Mount Bauple in southeast Queensland in Australia. Selective sweeps are detected in macadamia cultivars, including genes involved in fatty acid biosynthesis, seed coat development, and heat stress response. Such strong effects of artificial selection in few generations reveals the genomic basis for 'one-step operation' for clonal crop domestication. The knowledge gained could accelerate domestication of new crops from wild species.

A novel missense mutation of RPGR identified from retinitis pigmentosa affects splicing of the ORF15 region and causes loss of transcript heterogeneity.

Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, are the major cause of X-linked retinitis pigmentosa (RP), in which exon open reading frame 15 (ORF15) of RPGR has been implicated to play a substantial role. We identified a novel hemizygous missense mutation E585K of RPGR from whole-exome sequencing of RP. RNA-Seq analysis and functional study were conducted to investigate the underlying pathogenic mechanism of the mutation. Our results showed that the mutation actually affected RPGR ORF15 splicing. RNA-Seq analysis of the human retina followed by validation in cells revealed a complex splicing pattern near the 3' boundary of RPGR exon 14 in the ORF15 region, resulting from a variety of alternative splicing events (ASEs). The wildtype RPGR mini-gene expressed in human 293T cells confirmed these ASEs in vitro. In contrast, without new RNA species detected, the mutant mini-gene disrupted the splicing pattern of the ORF15 region, and caused loss of RPGR transcript heterogeneity. The RNA species derived from the mutant mini-gene were predominated by a minor out-of-frame transcript that was also observed in wildtype RPGR, resulting from an upstream alternative 5' splice site in exon 14. Our findings therefore provide insights into the influence of RPGR exonic mutations on alternative splicing of the ORF15 region, and the underlying molecular mechanism of RP.

Repeat Keratoplasty for Failed Therapeutic Keratoplasty for Microbial Keratitis: An Analysis of Characteristics and Risk Factors.

PURPOSE: To report the ratio of repeat-to-initial keratoplasty among patients who had underwent therapeutic keratoplasty for microbial keratitis in Southern China and to investigate the characteristics and risk factors of repeat keratoplasty. METHODS: A retrospective and inclusive review of the clinical records of patients who had received therapeutic keratoplasty for microbial keratitis, at Zhongshan Ophthalmic Center during December 2012 to January 2018, was performed. Patients who suffered coexistent endophthalmitis or underwent keratoplasty combined with other surgeries were excluded. Data on clinical characteristics of all eligible patients were collected. RESULTS: A total of 447 patients were identified. Their mean age was 48.7 ± 15.5 years, and 290 (64.9%) were male. Out of the 447 patients, 18 (4.0%) received repeat keratoplasty. Their mean age was 45.9 ± 11.3 years, and 14 (77.8%) were male. The most common indication of repeat keratoplasty (12/18) was refractory infectious keratitis. Most of the patients (15/18, 83.3%) received the second keratoplasty within 12 months after the initial keratoplasty. Factors, including age, gender, initial causative organism, presence of initial corneal perforation, ocular comorbidities, and surgical procedures were not found statistically significantly different between patients who received and not received repeat keratoplasty. CONCLUSION: The ratio of repeat-to-initial keratoplasty for therapeutic keratoplasty is low, compared to a failure rate of the initial grafts of over 50% reported in previous studies. The low ratio and the most common indication of repeat keratoplasty, refractory infectious keratitis, reflect caution for performing regrafts in such patients.

Effect of CPPU on Carbohydrate and Endogenous Hormone Levels in Young Macadamia Fruit.

N-(2-Chloro-4-pyridyl)-N'-phenylurea (CPPU) is a highly active cytokinin-like plant growth regulator that promotes chlorophyll biosynthesis, cell division, and cell expansion. It also increases fruit set and accelerates fruit enlargement. However, there has been no report about the effect of CPPU on fruit development and its physiological mechanism in macadamia. In this study, we investigated the effect of CPPU treatment at early fruit development via foliar spray or raceme soaking at 20 mg·L-1 on fruit set and related physiology in macadamia. Changes in carbohydrate contents and endogenous hormones in leaves, bearing shoots and fruit were also examined. Results showed that CPPU significantly reduced young fruit drop and delayed the wave of fruit drop by 1-2 weeks. The treatment significantly decreased the contents of total soluble sugars and starch in the leaves, but increased them in the bearing shoots and total soluble sugars in the husk (pericarp) and seeds. These findings suggested that CPPU promoted carbohydrate mobilization from the leaves to the fruit. In addition, CPPU increased the contents of indole-3-acetic acid (IAA), gibberellin acid (GA3), and zeatin riboside (ZR) and decreased the abscisic acid (ABA) in the husk. Therefore, CPPU treatment reduced the early fruit drop by increasing carbohydrate availability and by modifying the balance among endogenous hormones.