Loss of the proprioception and touch sensation channel PIEZO2 in siblings with a progressive form of contractures.

Dominant mutations in PIEZO2, which codes for the principal mechanotransduction channel for proprioception and touch sensation, have been found to cause different forms of distal arthrogryposis. Some observations suggest that these dominant mutations induce a gain-of-function effect on the channel. Here, we report a consanguineous family with three siblings who showed short stature, scoliosis, gross motor impairment, and a progressive form of contractures involving the distal joints that is distinct from that found in patients with dominant mutations in PIEZO2. These siblings also displayed deficits in proprioception and touch sensation. Whole-exome sequencing performed in the three affected siblings revealed the presence of a rare homozygous variant (c.2708C>G; p.S903*) in PIEZO2. This variant is predicted to disrupt PIEZO2 function by abolishing the pore domain. Sanger sequencing confirmed that all three siblings are homozygous whereas their parents and an unaffected sibling are heterozygous for this variant. Recessive mutations in PIEZO2 thus appear to cause a progressive phenotype that overlaps with, while being mostly distinct from that associated with dominant mutations in the same gene.

Comparative analysis of serum malondialdehyde, antioxidant vitamins and immunoglobulin levels in patients suffering from generalized anxiety disorder.

The relationship between the elevated levels of serum malondialdehyde, depleted level of antioxidants (vitamin A, E and C) and altered level of immunoglobulins (IgA, IgG and IgM) in several psychiatric disorders has been established by various experimental evidences over the past few years. But previously no study was carried out to determine these components in patients suffering from generalized anxiety disorder (GAD) in Bangladesh. This study was conducted to compare the serum concentration of these components in GAD patients and healthy volunteers; matched by socioeconomic and sociodemographic parameters. Serum level of malondialdehyde and vitamin C were determined by UV spectrophotometric method, vitamins A and E were detected by RP-HPLC method whereas immunoglobulin levels were determined by turbidimetric method. Data were analyzed by independent t-test, Pearson's correlation and regression analysis. Significantly lower level of vitamin E (p<0.05) and significantly higher level of vitamin C were found in GAD patients than the healthy controls, whereas the change of vitamin A was insignificant. Serum malondialdehyde content was significantly higher (p<0.05) and IgM level was significantly (p<0.05) higher than that of the controls. Change in concentrations of IgG and IgA were insignificant (p>0.05). Pearson's correlation coefficient suggested that there were some significant positive and negative correlations among these tested components. Our study reveals that GAD patients have considerably higher level of malondialdehyde, immunoglobulins and altered level of antioxidant vitamins. These findings may play a key role in the diagnosis and treatment of GAD patients.