Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis. 相似文献
Paroxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age dependence of the phenotypes has not been explored in detail in transgenic models. Here, we report our findings in heterozygous and homozygous Prrt2 knockout mice that recapitulate the age dependence of dyskinesia seen in the human disease. We show that Prrt2 deletion reduces the levels of synaptic proteins in a dose-dependent manner that is most pronounced at postnatal day 5 (P5), attenuates at P60, and disappears by P180. In a test for foot slippage while crossing a balance beam, transient loss of coordination was most pronounced at P60 and less prominent at age extremes. Slower traverse time was noted in homozygous knockout mice only, consistent with the ataxia seen in rare individuals with biallelic loss of function mutations in Prrt2. We thus identify three age-dependent phenotypic windows in the mouse model, which recapitulate the pattern seen in humans with PRRT2-related diseases.
[Purpose] This study investigated the intra-rater, inter-rater and test-retest
reliability of the sideways step test (SST), its correlation with other indicators of
stroke-specific impairment, and the cut-off count best discriminating subjects with stroke
from their healthy counterparts. [Subjects and Methods] Forty-three subjects with chronic
stroke and 41 healthy subjects older than 50 years participated in this study. The SST was
administered along with the Fugl-Meyer motor assessment for the lower extremities
(FMA-LE), the five-times sit to stand (5TSTS) test, the Berg Balance Scale (BBS), the
movement velocity (MVL) by the limits of stability (LOS) test, the ten-metre walk (10mW)
test, the timed “Up and Go” (TUG) test and the Activities-specific Balance Confidence
(ABC) scale. [Results] The SST showed good to excellent intra-rater, inter-rater and
test-retest reliability. The SST counts correlated with 5TSTS times, 10mW times, TUG
times, and the FMA-LE and BBS scores. SST counts of 11 for the paretic leg and 14 for the
non-paretic leg were found to distinguish the healthy adults from subjects with stroke.
[Conclusion] The sideways step test is a reliable clinical test, which correlates with the
functional strength, gait speed, and functional balance of people with chronic stroke.Key words: Balance, Stroke, Rehabilitation相似文献