Exome Sequencing Identifies a Mutation (Y740C) in Spastic Paraplegia 7 Gene Associated with Adult-Onset Primary Lateral Sclerosis in a Chinese Family.

BACKGROUND: Primary lateral sclerosis (PLS) is considered a rare variant of motor neuron disease (MND) characterized by selective upper motor neuron dysfunction leading to limb weakness, spasticity, and even bulbar symptoms. Previous studies have demonstrated that mutations in ALSIN, spastic paraplegia 7 (SPG7), TBK1, ALS2, ERLIN2, and FIG4 are responsible for PLS. Most of them occurred in childhood to young-adult onset patients. The aim of this study was to identify the genetic lesion of patients with adult-onset PLS. METHODS: We applied whole-exome sequencing (WES) and MND and ataxia-related genes filtering strategies to discover the genetic factors in a Chinese adult-onset PLS family. Sanger sequencing was used in the cosegregation analysis in the affected family members. RESULTS: A mutation (c.2219A>G/p.Y740C) in exon 17 of SPG7 was identified in an adult-onset PLS patient and cosegregated with the affected members in this family. Meanwhile, the mutation was predicted to be deleterious by 3 bioinformatics programs (Polymorphism phenotyping-2, sorting intolerant from tolerant and MutationTaster). This variant may cause the structure changes of paraplegin protein. CONCLUSIONS: We employed WES to detect a missense mutation of SPG7 gene in a PLS family. This finding expands the spectrum of known SPG7 mutations, and it may contribute to novel approaches to genetic diagnosis and counseling of families with PLS.

Effect of blood pressure variability on early neurological deterioration in single small subcortical infarction with parental arterial disease.

BACKGROUND AND PURPOSE: Early neurological deterioration (END) is not uncommon in acute single small subcortical infarct (SSSI), especially in those with parental arterial disease (PAD). The purpose of this study was to elucidate the effect of BP variability on the development of END as well as functional outcome at 90 days in SSSI and to determine whether the effect is linked to the status of parent artery. METHODS: Consecutive patients with acute SSSI were prospectively recruited from the First People's Hospital of Yangzhou between Aug 2013 and Jul 2016. END was defined as an NIHSS score increased ≥ 2 during the first 72 h compared with the initial NIHSS score. Functional outcome at 90 days after onset was assessed using the modified Rankin Score (mRS) and dichotomized as good (0-2) and poor (≥ 3). During this period, the parameters of BP variability such as BPmax-min, BPSD, and BPCV (equal to [SD × 100] / mean) were calculated. RESULTS: A total of 296 patients were included in the analysis. Of these, 30 (38.5%) SSSI associated with PAD and 53 (24.3%) without developed END respectively. Logistic regression analysis demonstrated that SBPmax (OR 1.036, 95% CI 1.005-1.069), SBPSD (OR 1.177, 95% CI 1.021-1.356), SBPcv (OR 1.306, 95% CI 1.049-1.626), DBPmax (OR 1.141, 95% CI 1.042-1.250), DBPmax-min (OR 1.085, 95% CI 1.015-1.160), DBPSD (OR 1.369, 95% CI 1.032-1.816), and DBPCV (OR 1.281, 95% CI 1.028-1.597) were all the independent predictors of END after acute SSSI associated with PAD. However, for those without PAD, none of the BP parameters was found significantly associated with END. Also, BP parameters were not related to the poor outcome at 90 days after onset. CONCLUSIONS: Our study demonstrated that the acute in-hospital BP variability was associated with the development of END in patients with acute SSSI. However, its impact varies depending on the status of parent artery.

Lesion patterns of single small subcortical infarct and its association with early neurological deterioration.

Early neurological deterioration (END), happening in the acute phase of infarct, is not rare in patients with single small subcortical infarction (SSSI). The aim of this study was to investigate the lesion patterns of SSSI and its association with END as well as functional outcome at 90 days after onset. 227 patients with acute SSSI in the perforator territory of MCA were prospectively recruited from Yangzhou No.1 People's Hospital between May 2010 and Jan 2014 and divided into proximal SSSI (pSSSI) and distal SSSI (dSSSI) according to the lesion patterns. END was defined as a change in National Institutes of Health Stroke Scale score ≥2 points in the first 72 h after admission. Functional outcome at 90 days after onset was assessed using the modified Rankin Score (mRS) and dichotomized as good (0-2) and poor (≥3). Of them, 93 (40.97%) patients had pSSSI and 134 (59.03%) patients had dSSSI. Univariate analysis found that the risk factors profiles differ significantly between patients with pSSSI and those with dSSSI (P < 0.05). During hospitalization, 60 (26.43%) patients experienced END during the first 72 h after admission, and 46 (22.01%) patients had poor outcome at 90 days after onset. After adjusting for potential confounders, pSSSI pattern (OR 2.242, 95% CI 1.165-4.313, P = 0.016) was an independent predictor of END and that the END (OR 2.637, 95% CI 1.208-5.759, P = 0.015) independently predicted the poor outcome at 90 days after onset. The pSSSI patterns might predict END for patients with SSSI in the MCA perforating territory.