Contribution of copy number variations in CMT1X: a retrospective study.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease type 1X (CMT1X) is an X-linked dominant hereditary motor-sensory peripheral neuropathy, which results from mutations in the Gap Junction B1 (GJB1) gene. In a few cases, gene deletions have been linked to the disease, but their relative contribution in the pathogenesis of CMT1X has not been assessed yet. Herein a retrospective study to establish the incidence of gene deletions is described. METHODS: Copy number variation analysis was performed by multiplex ligation-dependent probe amplification, whilst the breakpoints were defined by Sanger sequencing. RESULTS: A novel GJB1 deletion was identified in a family presenting with a classical CMT1X phenotype. The rearrangement includes the coding and the regulatory regions of GJB1. CONCLUSIONS: GJB1 deletions appear to be a rare but not insignificant cause of CMT1X and are associated with a typical disease phenotype. Accordingly, patients negative for point mutations whose pedigree and clinical records strongly suggest the possibility of CMT1X should be tested for GJB1 copy number variations.

The upper extremity and psychiatric illness.

Thirty-three patients who had various conversion reactions manifested by signs and symptoms involving the upper extremities were seen over a 13-year period. Factitious lymphedema, factitious ulcers, clenched fists, as well as other dysfunctional postures of the hand and upper extremity, were the most frequently recognized patterns of illness. Denial of knowledge of the cause of the physical problem and a lack of insight into the illness are major parts of the disease process. Twenty-nine of the 33 patients in this study had work-related and therefore compensable injuries. The physical signs and symptoms resolved in four of the patients when compensation was withdrawn. The average follow-up in this study was 4 1/2 years. Unfortunately, the long-term follow-up of these patients revealed that this disease process was chronic and most frequently failed to resolve. Various efforts at treatment have been unsuccessful, including extensive psychotherapy. Confrontation with the patient is contraindicated.

Validation of the saline-dilution method for measuring cardiac output by simultaneous measurement with a perivascular electromagnetic flowprobe.

The validity of measurements of right heart output obtained by the saline-indicator method with a catheter-mounted, tetrapolar resistivity sensor placed in the pulmonary artery was assessed. In ten anesthetized dogs, cardiac output was measured simultaneously by the saline-indicator method, using 5 ml of 3 per cent saline as the indicator, and by a perivascular electromagnetic flowprobe placed around the trunk of the pulmonary artery. Cardiac output was altered over a wide range by increasing the depth of halothane anesthesia and by bolus injections of isoproterenol. Linear regression analysis of cardiac output determined from 455 saline-indicator curves and from simultaneous recordings of the electromagnetic flow signal yielded a slope of 0.973, a Y intercept of -0.0047 1/minute, and a correlation coefficient of 0.965. Hence, this method provides accurate and precise measurement of cardiac output. The saline-indicator method with the catheter-mounted resistivity sensor is simple to use and eliminates or minimizes the disadvantages of other indicator-dilution techniques.

Thermographic evaluation of horses with podotrochlosis.

The distal forelimbs of 10 clinically normal horses with hair clipped on 1 limb were thermographically scanned before and after exercise. The thermal patterns, temperature distribution, and temperature changes after exercise were determined and compared with those of 8 horses with podotrochlosis. Clipping the hair did not cause changes in the thermal patterns, but the clipped limbs were warmer than the unclipped limbs. The temperature of the limbs of horses with podotrochlosis did not increase as much after exercise as did the limbs of normal horses. The failure of skin temperature increase correlated with the radiographic evidence of enlarged vascular foramina in the navicular bone. Because the failure to increase skin temperature after exercise is the result of low blood flow, the enlarged vascular foramen can be related to a state of low blood flow.