关键词： CALHM2   CALHM5   Channel   ATP   Gap junction  

摘要： Recently calcium homeostasis modulators (CALHMs) are identified as ATP release channels play crucial role in functioning of neurons including gustatory signaling and neuronal excitability. Pathologies of Alzheimer's disease and depression have been associated with the dysfunction of CALHMs. Recently, CALHMs has been emerged as an important therapeutic research particularly in neurobiological studies. CALHM1 is most extensively studied among CALHMs and is an ATP and ion channel that is activated by membrane depolarization or removal of extracellular Ca2+. Despite the emerged role of CALHM5 shown by an recently assembled data;however, the neuronal function remains obscure until the first Cryo-EM structure of CALHM5 was recently solved by various research group which acts as a template to study the hidden functional properties of the CALHM5 protein based on structure function mechanism. It provides insight in some of the different pathophysiological roles. CALHM5 structure showed an abnormally large pore channel structure assembled as an undecamer with four transmembrane helices (TM1-TM4), an N-terminal helix (NTH), an extracellular loop region and an intracellular C-terminal domain (CTD) that consists of three alpha-helices CH1-3. The TM1 and NTH were always poorly defined among all CALHMs;however, these regions were well defined in CALHM5 channel structure. In this context, this review will provide insight in structure, function and mechanism to understand its significant role in pathological diseases particularly in Alzheimer's disease. Moreover, it focuses on CALHM5 structure and recent associated properties based on Cryo-EM research. [GRAPHICS] .

关键词： Genetic counseling   Variant of uncertain significance (VUS)   Variant reclassification   Pediatrics   Genetic testing  

摘要： Improvements in technology used for genetic testing have yielded an increased numbers of variants that are identified, each with a potential to return uninformative results. While some genetics providers may expect patients to be responsible for staying abreast of updates to their genetic testing results, it is unknown whether patients are even aware of the possibility of variant reclassification. Little research has assessed the comprehension and attitudes of parents of pediatric patients regarding reclassification of variants of uncertain significance (VUS). Semi-structured telephone interviews were conducted with parents (n = 15) whose children received a VUS from genetic testing in either the pediatric neurogenetics or developmental pediatrics clinics at Riley Hospital for Children in Indianapolis, Indiana. Most participants expressed understanding of the uncertainty surrounding their child's VUS test result. However, nearly half of participants shared that they had no prior knowledge of its potential reclassification. When asked whose responsibility it is to keep informed about changes to their child's VUS status, some participants stated that it belonged solely to healthcare providers - a distinctive finding of our study - whereas others felt that it was a joint responsibility between providers and the parents. We additionally found that some patients desire a support group for individuals with VUS. These results provide insight into the importance of pretest genetic counseling and the need for increased social and informational support for parents of children who receive inconclusive genetic testing results. We conclude that relying solely on the patient or guardian to manage uncertain results may be insufficient.