De novo variants in SUPT16H cause neurodevelopmental disorders associated with corpus callosum abnormalities.

INTRODUCTION: Whole-exome sequencing (WES) has identified de novo variants in chromatin remodelling genes in patients with neurodevelopmental disorders (NDD). We report on a novel genetic discovery in chromatin remodelling in patients with NDD who also have corpus callosum (CC) anomalies. OBJECTIVE: To discover novel genes linked to both CC anomalies and NDD. METHODS: Clinical WES was performed for evaluation of NDD, identifying five patients with de novo variants in SUPT16H, a subunit of the FACT (facilitates chromatin transcription) complex. The clinical phenotypes, genetic results and brain MRIs were obtained and systematically reviewed. In silico protein function predictions were assessed and allele frequencies in control populations were compared. RESULTS: We identified four patients with de novo missense variants in SUPT16H and one patient with a de novo deletion including SUPT16H. These variants were not reported in the updated Genome Aggregation Database. When assayable, all protein products were predicted to be damaging. Symptoms included intellectual disability, autistic features, minor dysmorphic features and seizures. Anomalies of the CC were seen in all three patients with available brain imaging. CONCLUSION: Our findings implicate the gene SUPT16H in a novel disorder characterised by neurodevelopmental deficits and CC anomalies.

Median and ulnar nerve injuries; what causes different repair outcomes?

BACKGROUND: Peripheral nerve injuries have significant effects on patients' life quality. To make patients' therapeutic expectations more realistic, prediction of repair outcome has significant importance. MATERIALS AND METHODS: Totally, 74 patients with 94 nerve injuries (44 median and 50 ulnar nerves) were evaluated and followed up for 5 years between 2008 and 2013 in two main university hospitals of Isfahan. Patients' age was 6-64 years. 24 nerves were excluded from the study and among the remaining; 53 nerves were repaired primarily and 17 nerves secondarily. 42 nerves were injured at a low-level, 17 nerves at intermediate and 11 at a high one. Medical Research Council Scale used for sensory and motor assessment. S3+ and S4 scores for sensory recovery and M4 and M5 scores for motor recovery were considered as favorable results. The follow-up time was between 8 and 24 months. RESULTS: There was no significant difference between favorable sensory outcomes of median and ulnar nerves. The difference between favorable motor outcomes of the median nerve was higher than ulnar nerve (P = 0.03, odds ratio = 2.9). More favorable results were seen in high-level injuries repair than low ones (P = 0.035), and also cases followed more than 18 months compared to less than 12 months (P = 0.041), respectively. The favorable outcomes for patients younger than 16 were more than 40 and older, however, their difference was not significant (P = 0.059). The difference between primary and secondary repair favorable outcomes was not significant (P = 0.37). CONCLUSION: In patients older than 40 or injured at a high-level, there is a high possibility of repetitive operations and reconstructive measures. The necessity for long-term follow-up and careful attentions during a postoperative period should be pointed to all patients.

Venous insufficiency after prolonged standing: Is joint hypermobility an important risk factor?

BACKGROUND: Varicose veins are extremely common disease which is due to elevated superficial venous pressures. We aimed to know that if joint hypermobility causes the venous insufficiency following the prolonged standing. MATERIALS AND METHODS: This prospective cohort study conducted on the soldiers of training periods in a military base of Iran Army in Isfahan in 2013. The active-duty soldiers were first examined by a physician and their Beighton scores (BSs) were obtained. At the onset of the training period, the presence of chronic venous insufficiency was clinically evaluated according to the C class of clinical, etiological, anatomical, and pathological classification. After 3 months, soldiers with and without joint hypermobility were reexamined for manifestations of venous insufficiency based on clinical examination. RESULTS: Of 718 soldiers, 211 subjects were diagnosed for joint hypermobility syndrome (29.3%). The mean BS was significantly higher in hypermobility soldiers (5.5 ± 1.5) than the healthy ones (1.2 ± 1.1). Before the training period, the prevalence of spider and varicose veins in soldiers with joint hypermobility was significantly higher than healthy subjects (P > 0.001). After the training period, the prevalence of venous insufficiency significantly increased in soldiers with joint hypermobility (P > 0.001) while there was no significant difference in healthy group before and after the period of training (P = 0.25). CONCLUSION: Hypermobility could be considered as a risk factor for the development of venous insufficiency, so it seems necessary to evaluate the population who need to be standing for a long time for evidence of joint hypermobility.