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Background: The identification of disease causing, or putative disease causing, mutations in index patients with Charcot-Marie-Tooth disease (CMT) allows for genetic testing of family members. Relevant variants identified in index patients are of either definite, likely or uncertain pathogenicity. The main objective of this study was to make an evaluation of the family investigations performed as part of the assessment of genetic variants of unknown clinical significance (VUS)., Methods: Between 2004 and 2010 molecular genetic family investigations were requested for 87 family members from 41 families harbouring PMP22dup or genetic variants in GJB1, MPZ, MFN2 and NEFL. Relatives were tested for the family mutation and data from the requisitions were evaluated by means of statistical tools., Results: The results within each indication category are presented and discussed in detail. Twenty-two relatives (9 affected) from eight families were included in the segregation analyses, which invoked reclassification of three MFN2 mutations, two of which were de novo substitutions (c.2146_2148dup, c.692C > T). One MFN2 substitution was downgraded due to non-segregation (c.1709 A > G), and a MPZ substitution (c.103 G > A) upgraded due to segregation with the phenotype in the family., Conclusions: The results allow for the evaluation of the patient phenotypes ascertained in families, as opposed to the phenotypic descriptions of index patients. They indicate that de novo MFN2 mutations are regularly found in patients with a classical CMT2 phenotype. They also demonstrate the importance of a precise clinical and neurophysiologic diagnosis of affected family members. This particularly applies for the examination of variants of uncertain clinical significance. Finally, the fact that 14,6% of affected relatives tested for (probable or certain) pathogenic mutations were mutation negative, demonstrates that clinical evaluation alone is not always sufficient in order to determine their diagnosis. We believe that the results will aid in the estimation and planning of resources required for the various aspects of family evaluations in CMT.

Background: Current genetic test algorithms for Charcot Marie Tooth (CMT) disease are based on family details and comprehensive clinical and neurophysiological data gathered under ideal conditions for clinical assessment. However, in a diagnostic laboratory setting relying on external test requisitions and patient samples, such conditions are not always met. Our objective was therefore to perform a retrospective evaluation of the data given in laboratory request forms and to assess their quality and applicability with regard to the recommended algorithms for CMT diagnostics. As we are the main test centre for CMT in Norway our results also provide an overview of the spectrum of gene defects in the Norwegian CMT population., Methods: Genetic testing was performed according to polyneuropathy type; demyelinating/mixed: PMP22 duplication, MPZ, EGR2, LITAF, NEFL, PMP22, GJB1, axonal: MFN2, MPZ, NEFL, and GJB1., Results: Diagnostic testing of index patients was requested in 435 of the 549 cases. Seventy-two (16.6%) positive molecular genetic findings were made. The majority (94.6%) of mutation positive cases showed disease onset before 50 years of age. PMP22 (duplication), MPZ, GJB1 and MFN2 mutations constituted 95.8% of the positive findings. Within the nerve conduction study groups, mutation detection rates were; demyelinating 33.8%; mixed 29.0%; axonal 8.8%; unspecified 16.5%., Conclusion: We suggest a simplified algorithm intended for referral centres, dealing with DNA/blood samples, which involves the assessment of age at onset and neurophysiological data followed by testing of four genes; PMP22 (duplication), MPZ, GJB1 and MFN2. Patients negative for mutations in those four genes should be subjected to evaluation at an interdisciplinary inherited neuropathy clinic with the capacity for extended molecular genetic analysis by next generation sequencing.

Introduction: Chlamydia is the most common sexually transmitted bacterial infection in Denmark. Each year 13-14,000 cases are diagnosed; of these about 3000 occur in men. In order to describe the prevalence of chlamydia among young men, screening for chlamydia was conducted in those liable for military service and coming before the medical board., Materials and Methods: Of 2500 men coming before the medical boards in North Jutland State County, Arhus State County, and Copenhagen County during the winter of 1996-97, 1345 men aged 17-32 (median 18 years) were entered in the study. The participants sent a urine sample and a filled-in questionnaire to Statens Serum Institut. The urine samples were analysed by an in-house PCR and the test results were sent to the participant; if permission had been granted, the positive test results were further sent to the general practitioner, along with a second questionnaire., Results: Chlamydia was found in 4.8% (65/1345) of all participants and in 6.9% of those sexually active. In North Jutland State County 7.1 and 9.8%, respectively, had chlamydia, whereas the corresponding figures for Arhus State County and Copenhagen County were about 4% and 6%. Two-thirds of the patients had no symptoms of urethritis., Discussion: The results of this study indicate that a considerable reservoir of unrecognised chlamydia must exist in young men. The prevalence of chlamydia was higher in North Jutland State County than in the other two districts. One explanation could be that there is more focus on sexually transmitted infections and contact tracing in the largest cities than in the rest of the country.

Introduction: Urogenital chlamydia is still common in the young. The late risks are well-documented. Most of the infections are diagnosed in general practice. The aim was to assess general practitioners' handling of urogenital chlamydial infections in young people aged 15-25 years., Methods: Two groups of GPs were selected at random and were asked to complete a questionnaire before and after a "State-of-the-Art" was sent to all GPs from the National Board of Health. The questionnaire covered questions about 1) the test indication; 2) advice on the infection diagnosed; 3) contact tracing; and 4) first choice of treatment for uncomplicated infection in non-pregnant women., Results: There was no difference between the two groups in the answers to questions 1) to 3), but an obvious change towards single-dose treatment in question 4), not because of the "State-of-the-Art", but rather because of the intensive marketing of the simple treatment regime., Discussion: Implementation of new knowledge in general practice does not work only through national guidelines from the authorities to general practice, but is wholly dependent on central and local collaboration and GPs having the chance to discuss it between themselves.

In order to determine observer variation in the assessment of the thyroid gland by ultrasonography, two specialists (one endocrinologist and one radiologist) independently evaluated 76 thyroid glands, and assessed the sonogram as homogeneous, inhomogeneous, containing a solitary solid lesion or a solitary cyst in each of 152 thyroid lobes. The observed agreement between the two observers ranged from 0.80 to 0.91. By the use of the kappa coefficient the observed agreement was adjusted for change agreement. Kappa can vary from -1 (total disagreement) to +1 (total agreement) and kappa values between 0.55 and 0.60 were found. Among 152 lobes a solitary solid lesion, i.e. a nodule, was found in 22 lobes by the two observers; however, they only agreed on a classification in 10 lobes (45%). Clinicians should be aware of the moderate agreement between observers in thyroid ultrasonography.