Two novel connexin32 mutations cause early onset X-linked Charcot-Marie-Tooth disease

<p>Abstract</p> <p>Background</p> <p>X-linked Charcot-Marie Tooth (CMT) is caused by mutations in the connexin32 gene that encodes a polypeptide which is arranged in hexameric array and form gap junctions.</p> <p>Methods</p> <p>We describe two novel mutations in the connexin32 gene in two Norwegian families.</p> <p>Results</p> <p>Family 1 had a c.225delG (R75fsX83) which causes a frameshift and premature stop codon at position 247. This probably results in a shorter non-functional protein structure. Affected individuals had an early age at onset usually in the first decade. The symptoms were more severe in men than women. All had severe muscle weakness in the legs. Several abortions were observed in this family. Family 2 had a c.536 G>A (C179Y) transition which causes a change of the highly conserved cysteine residue, i.e. disruption of at least one of three disulfide bridges. The mean age at onset was in the first decade. Muscle wasting was severe and correlated with muscle weakness in legs. The men and one woman also had symptom from their hands.</p> <p>The neuropathy is demyelinating and the nerve conduction velocities were in the intermediate range (25–49 m/s). Affected individuals had symmetrical clinical findings, while the neurophysiology revealed minor asymmetrical findings in nerve conduction velocity in 6 of 10 affected individuals.</p> <p>Conclusion</p> <p>The two novel mutations in the connexin32 gene are more severe than the majority of previously described mutations possibly due to the severe structural change of the gap junction they encode.</p

Classification of bipolar disorder in psychiatric hospital. a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>This study has explored the classification of bipolar disorder in psychiatric hospital. A review of the literature reveals that there is a need for studies using stringent methodological approaches.</p> <p>Methods</p> <p>480 first-time admitted patients to psychiatric hospital were found eligible and 271 of these gave written informed consent. The study sample was comprised of 250 patients (52%) with hospital diagnoses. For the study, expert diagnoses were given on the basis of a structured diagnostic interview (M.I.N.I.PLUS) and retrospective review of patient records.</p> <p>Results</p> <p>Agreement between the expert's and the clinicians' diagnoses was estimated using Cohen's kappa statistics. 76% of the primary diagnoses given by the expert were in the affective spectrum. Agreement concerning these disorders was moderate (kappa ranging from 0.41 to 0.47). Of 58 patients with bipolar disorder, only 17 received this diagnosis in the clinic. Almost all patients with a current manic episode were classified as currently manic by the clinicians. Forty percent diagnosed as bipolar by the expert, received a diagnosis of unipolar depression by the clinician. Fifteen patients (26%) were not given a diagnosis of affective disorder at all.</p> <p>Conclusions</p> <p>Our results indicate a considerable misclassification of bipolar disorder in psychiatric hospital, mainly in patients currently depressed. The importance of correctly diagnosing bipolar disorder should be emphasized both for clinical, administrative and research purposes. The findings questions the validity of psychiatric case registers. There are potential benefits in structuring the diagnostic process better in the clinic.</p

Two novel missense mutations in the myelin protein zero gene causes Charcot-Marie-Tooth type 2 and Déjérine-Sottas syndrome

<p>Abstract</p> <p>Background</p> <p>The Charcot-Marie-Tooth (CMT) phenotype caused by mutation in the <it>myelin protein zero (MPZ) </it>gene varies considerably, from early onset and severe forms to late onset and milder forms. The mechanism is not well understood. The myelin protein zero (P₀) mediates adhesion in the spiral wraps of the Schwann cell's myelin sheath. The crystalline structure of the extracellular domain of the myelin protein zero (P₀ex) is known, while the transmembrane and intracellular structure is unknown.</p> <p>Findings</p> <p>One novel missense mutation caused a milder late onset CMT type 2, while the second missense mutation caused a severe early onset phenotype compatible with Déjérine-Sottas syndrome.</p> <p>Conclusions</p> <p>The phenotypic variation caused by different missense mutations in the <it>MPZ </it>gene is likely caused by different conformational changes of the MPZ protein which affects the functional tetramers. Severe changes of the MPZ protein cause dysfunctional tetramers and predominantly uncompacted myelin, i.e. the severe phenotypes congenital hypomyelinating neuropathy and Déjérine-Sottas syndrome, while milder changes cause the phenotypes CMT type 1 and 2.</p

The effect of temperature on growth and competition between Sphagnum species

Peat bogs play a large role in the global sequestration of C, and are often dominated by different Sphagnum species. Therefore, it is crucial to understand how Sphagnum vegetation in peat bogs will respond to global warming. We performed a greenhouse experiment to study the effect of four temperature treatments (11.2, 14.7, 18.0 and 21.4°C) on the growth of four Sphagnum species: S. fuscum and S. balticum from a site in northern Sweden and S. magellanicum and S. cuspidatum from a site in southern Sweden. In addition, three combinations of these species were made to study the effect of temperature on competition. We found that all species increased their height increment and biomass production with an increase in temperature, while bulk densities were lower at higher temperatures. The hollow species S. cuspidatum was the least responsive species, whereas the hummock species S. fuscum increased biomass production 13-fold from the lowest to the highest temperature treatment in monocultures. Nutrient concentrations were higher at higher temperatures, especially N concentrations of S. fuscum and S. balticum increased compared to field values. Competition between S. cuspidatum and S. magellanicum was not influenced by temperature. The mixtures of S. balticum with S. fuscum and S. balticum with S. magellanicum showed that S. balticum was the stronger competitor, but it lost competitive advantage in the highest temperature treatment. These findings suggest that species abundances will shift in response to global warming, particularly at northern sites where hollow species will lose competitive strength relative to hummock species and southern species

Estimating the number of children exposed to parental psychiatric disorders through a national health survey

<p>Abstract</p> <p>Objective</p> <p>Children whose parents have psychiatric disorders experience an increased risk of developing psychiatric disorders, and have higher rates of developmental problems and mortality. Assessing the size of this population is important for planning of preventive strategies which target these children.</p> <p>Methods</p> <p>National survey data (CCHS 1.2) was used to estimate the number of children exposed to parental psychiatric disorders. Disorders were diagnosed using the World Psychiatric Health Composite International Diagnostic Interview (WMH-CIDI) (12 month prevalence). Data on the number of children below 12 years of age in the home, and the relationship of the respondents with the children, was used to estimate exposure. Parent-child relations were identified, as was single parenthood. Using a design-based analysis, the number of children exposed to parental psychiatric disorders was calculated.</p> <p>Results</p> <p>Almost 570,000 children under 12 live in households where the survey respondent met criteria for one or more mood, anxiety or substance use disorders in the previous 12 months, corresponding to 12.1% of Canadian children under the age of 12. Almost 3/4 of these children have parents that report receiving no mental health care in the 12 months preceding the survey. For 17% of all Canadian children under age 12, the individual experiencing a psychiatric disorder is the only parent in the household.</p> <p>Conclusion</p> <p>The high number of children exposed causes major concern and has important implications. Although these children will not necessarily experience adversities, they possess an elevated risk of accidents, mortality, and of developing psychiatric disorders. We expect these estimates will promote further research and stimulate discussion at both health policy and planning tables.</p