Lynch syndrome in South America: past,present and future

After decades of unawareness about Lynch syndrome, the medical community in South America is increasingly interested and informed. The visits and support of mentors like H. T. Lynch had been crucial to this awakening. Several countries have at least one registry with skilled personnel in genetic counseling and research. However, this only represents a very restricted resource for the region. According to the GETH, there are 27 hereditary cancer care centers in South America (21 in Brazil, 3 in Argentina, 1 in Uruguay, 1 in Chile and 1 in Peru). These registries differ in fundamental aspects of function, capabilities and funding, but are able to conduct high quality clinical, research and educational activities due to the dedication and personal effort of their members, and organizational support. More support from the governments as well as the participation of the community would boost the initiatives of people leading these groups. Meantime, the collaboration among the South American registries and the involvement of registries and leaders from developed countries will allow to maximize the efficiency in caring for affected patients and their families. The aim of this article is to describe how the knowledge of LS began to be spread in South America, how the first registries were organized and to summarize the current state of progress. In addition, we will provide an update of the clinical and molecular findings in the region.     

Exploring the functional role of the CHRM2 gene in human cognition: results from a dense genotyping and brain expression study

Background  

The CHRM2 gene, located on the long arm of chromosome 7 (7q31-35), is involved in neuronal excitability, synaptic plasticity and feedback regulation of acetylcholine release, and has been implicated in higher cognitive processing. The aim of this study is the identification of functional (non)coding variants underlying cognitive phenotypic variation.     

Impaired Bone Microarchitecture Improves After One Year On Gluten‐Free Diet: A Prospective Longitudinal HRpQCT Study in Women With Celiac Disease

We have recently identified a significant deterioration of bone microarchitecture in premenopausal women with newly diagnosed celiac disease (CD) using high‐resolution peripheral quantitative computed tomography (HRpQCT). The aim of this work was to assess changes in bone microarchitecture after 1 year on a gluten‐free diet (GFD) in a cohort of premenopausal women. We prospectively enrolled 31 consecutive females at diagnosis of CD; 26 of them were reassessed 1 year after GFD. They all underwent HRpQCT scans of distal radius and tibia, areal BMD by DXA, and biochemical tests (bone‐specific parameters and CD serology) at both time points. Secondary, we compared 1‐year results with those of a control group of healthy premenopausal women of similar age and BMI in order to assess whether the microarchitectural parameters of treated CD patients had reached the values expected for their age. Compared with baseline, the trabecular compartment in the distal radius and tibia improved significantly (trabecular density, trabecular/bone volume fraction [BV/TV] [p < 0.0001], and trabecular thickness [p = 0.0004]). Trabecular number remained stable in both regions. Cortical density increased only in the tibia (p = 0.0004). Cortical thickness decreased significantly in both sites (radius: p = 0.03; tibia: p = 0.05). DXA increased in all regions (lumbar spine [LS], p = 0.01; femoral neck [FN], p = 0.009; ultradistal [UD] radius, p = 0.001). Most parameters continued to be significantly lower than those of healthy controls. This prospective HRpQCT study showed that most trabecular parameters altered at CD diagnosis improved significantly by specific treatment (GFD) and calcium and vitamin D supplementation. However, there were still significant differences with a control group of women of similar age and BMI. In the prospective follow‐up of this group of patients we expect to be able to assess whether bone microarchitecture attains levels expected for their age. © 2016 American Society for Bone and Mineral Research.     

HLA-B62 and HLA-DQ8 are associated with Complex Regional Pain Syndrome with fixed dystonia

Complex Regional Pain Syndrome (CRPS) is clinically characterized by pain in combination with sensory, autonomic, and motor symptoms that may include weakness, tremor, myoclonus and dystonia of the affected limb(s). The syndrome is multifactorial in origin and mostly attributed to tissue injury. There is some evidence that the human leukocyte antigen (HLA) system plays a role in the pathophysiology of CRPS, but previous studies lacked power. Here we performed the most extensive study investigating the contribution of HLA alleles (i.e. HLA-A, HLA-B, HLA-DRB1, and HLA-DQB1) in 150 CRPS patients who also had fixed dystonia. HLA-B62 (OR = 2.05 [95% CI 1.41–2.99], P = 0.0005) and HLA-DQ8 (OR = 1.75 [95% CI 1.20–2.57], P = 0.005) were found significantly associated with CRPS and dystonia. The association remained significant after correction (HLA-B62 P_corrected [P_c] = 0.02 and HLA-DQ8 P_c = 0.04). The involvement of HLA-B62 and HLA-DQ8 in CRPS with dystonia may indicate that these HLA loci are implicated in the susceptibility or expression of the disease.