Mucopolysaccharidosis type II in a female patient with a reciprocal X;9 translocation and skewed X chromosome inactivation.

Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme, iduronate-2-sulfatase (IDS). Phenotypic expression of MPS II in female patients rarely occurs and may be the result of (i) structural abnormalities of the X chromosome, (ii) homozygosity for disease-causing mutations, or (iii) skewed X-chromosome inactivation, in which the normal IDS allele is preferentially inactivated and the abnormal IDS allele is active. We report here on a female patient with clinical MPS II manifestations, deficiency of IDS enzyme activity and a de novo balanced reciprocal X;9 translocation. As our patient has a skewed XCI pattern, but neither genomic IDS mutations nor abnormal IDS transcripts were detected, we speculate about the possible role of the chromosomal rearrangement in reducing the IDS translation efficiency.

Clinical and molecular cross-sectional study of a cohort of adult type III spinal muscular atrophy patients: clues from a biomarker study.

Proximal spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations of the SMN1 gene. Based on severity, three forms of SMA are recognized (types I-III). All patients usually have 2-4 copies of a highly homologous gene (SMN2), which produces insufficient levels of functional survival motor neuron (SMN) protein due to the alternative splicing of exon 7. The availability of potential candidates to the treatment of SMA has raised a number of issues, including the availability of biomarkers. This study was aimed at evaluating whether the quantification of SMN2 products in peripheral blood is a suitable biomarker for SMA. Forty-five adult type III patients were evaluated by Manual Muscle Testing, North Star Ambulatory Assessment scale, 6-min walk test, myometry, forced vital capacity, and dual X-ray absorptiometry. Molecular assessments included SMN2 copy number, levels of full-length SMN2 (SMN2-fl) transcripts and those lacking exon 7 and SMN protein. Clinical outcome measures strongly correlated to each other. Lean body mass correlated inversely with years from diagnosis and with several aspects of motor performance. SMN2 copy number and SMN protein levels were not associated with motor performance or transcript levels. SMN2-fl levels correlated with motor performance in ambulant patients. Our results indicate that SMN2-fl levels correlate with motor performance only in patients preserving higher levels of motor function, whereas motor performance was strongly influenced by disease duration and lean body mass. If not taken into account, the confounding effect of disease duration may impair the identification of potential SMA biomarkers.

Optimal site for atrial lead implantation in myotonic dystrophy patients: the role of Bachmann's Bundle stimulation.

AIM: The aim of this study was to identify the optimal site for atrial lead implantation in myotonic dystrophy type 1 (MD1) patients. METHODS: The atrial pacing lead was positioned in the high-lateral right atrial wall (site A), then in the right atrial appendage (site B), and finally on the interatrial septum (site C) in 22 patients. Pacing and sensing thresholds were obtained for all sites. The lead was repositioned and fixed at the optimal site, defined as the location with the lowest pacing and the highest sensing thresholds. RESULTS: Mean pacing thresholds were 1.46 +/- 0.32 V at site A, 1.45 +/- 0.33 V at site B, and 0.84 +/- 0.24 V at site C. P-wave amplitude was 1.52 +/- 0.45 mV at site A, 1.52 +/- 0.49 mV at site B, and 2.60 +/- 0.48 mV at site C. Atrial lead was implanted at site C in all patients without complications. CONCLUSIONS: Interatrial septum in the region of Bachmann's Bundle seems to be the optimal site for atrial lead implantation in MD1 patients.