Chinese patients with distal hereditary motor neuropathy: An analysis of clinical characteristics / 第二军医大学学报

Objective: To evaluate the clinical characteristics of Chinese patients with distal hereditary motor neuropathy (dHMN). Methods: The clinical data on patients with dHMN collected from literatures published in China and from the patients treated in our hospital were retrospectively analyzed. Results: The male to female ratio of patients was 1.32 : 1. The age of onset was from 13 to 60 years old, with a mean of (38.2±10.4) years old. The incidences of onset from the lower limbs, the upper limbs, and the four limbs were 84.7% 5.6%, and 9.7%, respectively. The incidences of decreased tendon reflexes, lost tendon reflexes in the upper limbs, decreased tendon reflexes and lost tendon reflexes in the upper limbs were 30.4% 65.3%, 13.0%, and 87.0%, respectively. The incidences of grade 3-4, grade 2, and grade 0-1 muscle strength of the upper limbs, grade 3-4, grade 2, and grade 0-1 muscle strength of the lower limbs were 55.4%, 37.5%, 7.1%, 50.0%, 37.5%, and 12.5%, respectively. No sensory disturbance was found in the patients. Electromyography (EMG) of 26 patients showed neurogenic damages; the motor and sensory nerve conduction velocities were all normal. Eight patients showed neurogenic amyotrophy in muscular biopsy. Conclusion: The onset of dHMN is mainly at middle-age and mainly in the lower limbs. The major manifestations include weakness and atrophy of distal limb muscles, decreased or lost tendon reflexes without sensory loss. Electrophysiology and pathology examinations play an important role in the diagnosis of dHMN.

Study on aggregate formation mechanism of HSPB8 gene mutation resulting in CMT2L / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the possible mechanism of the intracellular aggregate formation of small heat shock protein HSPB8 (HSPB8)(K141N) mutation resulting in axonal Charcot-Marie-Tooth disease type 2L(CMT2L).</p><p><b>METHODS</b>The cell models which transiently expressed pEGFPN1-HSPB8 and pEGFPN1-(K141N)HSPB8 were established. The immunofluorescent co-location study of EGFP-(K141N)HSPB8 and HSPB1, EGFP-(K141N)HSPB8 and neurofilament light chain (NEFL) was carried out in the SHSY5Y cell models. The aggregate formation of EGFP-(K141N)HSPB8 in cell models was investigated and the possible mechanism of cellular aggregate formation was analyzed by t test and analysis of variance between group(ANOVA).</p><p><b>RESULTS</b>EGFP-(K141N)HSPB8 formed large aggregate which predominantly located around the nucleus in cell models. EGFP-(K141N)HSPB8 co-localized perfectly with HSPB1 and NEFL in the SHSY5Y cell models. The aggregate formation was different in different cell types, there were fewer aggregates formed in an sHSPs deficient milieu than in HEK293T cells.</p><p><b>CONCLUSION</b>(K141N)HSPB8 formed aggregates predominantly locate around the nucleus in cells. (K141N)HSPB8 co-localizes perfectly with HSPB1 and NEFL. The aggregate formation may be due to (K141N)HSPB8 conformational change leading to self aggregation and its abnormal interaction with other sHSPs such as HSPB1.</p>

Clinical, pathological and genetic studies in a Chinese Charcot-Marie-Tooth disease type 2 family / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To report a Chinese Charcot-Marie-Tooth disease type 2 (CMT2) family.</p><p><b>METHODS</b>All the members in the family were studied clinically,and 6 patients were studied electrophysiologically. Sural nerve biopsy was performed in the proband. PMP22 gene duplications were detected by highly polymorphic short tandem repeat. Point mutation analysis of PMP22, MPZ and NEFL gene was screened by PCR-SSCP combined with DNA direct sequencing. A genome-wide screening was carried out to the family.</p><p><b>RESULT</b>Except 2 who had weakness and atrophy in both proximal and distal muscles of the lower limbs, all patients presented muscle wasting and a predominating weakness of distal parts of the lower limbs, and mild to moderate sensory impairments. In 6 patients who were subjected to elctrophysiological examinations, median-nerve conduction velocity (NCV) of the median nerve was normal. Electromyograms (EMGs) revealed signs of denervation with large motor unit potentials, fibrillation potentials and positive sharp waves. Sural nerve biopsy of the proband confirmed the presence of axonal neuropathy with an important loss of large myelinating fibers and a large number of clusters with mostly thinly myelinated axons. PMP22, MPZ and NEFL gene mutations were not found. The results of genome-wide screening revealed a linkage of CMT2 to a locus at chromosome 12q24.</p><p><b>CONCLUSION</b>The results are consistent with the diagnosis of CMT2. This family represents a rare genetic type of CMT2 which can be designated as CMT2L.</p>

Mutation analysis of small heat-shock protein 22 gene in Chinese patients with Charcot-Marie-Tooth disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the characteristics of the mutation of small heat-shock protein 22 (HSP22) gene in Chinese patients with Charcot-Marie-Tooth (CMT) disease.</p><p><b>METHODS</b>A CMT2L proband with 423(G--> T) mutation in HSP22 gene had been studied and reported by the present authors. In this study, mutation analysis of HSP22 gene was performed using polymerase chain reaction and DNA direct sequencing in 114 CMT probands.</p><p><b>RESULTS</b>In the 114 CMT probands, a 582(C--> T)(T194T)samesense mutation was found in two unrelated families.</p><p><b>CONCLUSION</b>The rate of HSP22 gene mutation in Chinese patients with CMT is as low as 0.87%(1/115).</p>

Mutation analysis of small heat shock protein 27 gene in Chinese patients with Charcot-Marie-Tooth disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the features of small heat shock protein 27 (HSP27) gene mutation in Chinese patients with Charcot-Marie-Tooth disease (CMT).</p><p><b>METHODS</b>DNA samples from 114 CMT probands were screened for mutations in HSP27 gene by polymerase chain reaction and direct sequencing, and haplotype analysis was further carried out on the mutation detected families.</p><p><b>RESULTS</b>One missense mutation C379T was detected in 4 autosomal dominant CMT2 families. Haplotype analysis indicated that the 4 families probably had a common ancestor.</p><p><b>CONCLUSION</b>To the authors' knowledge, this is the first report of HSP27 gene mutation in Chinese patients with CMT, but it may be not common(0.90%). The C379T mutation in HSP27 gene also causes CMT2 except for distal hereditary motor neuropathy, thus providing further evidence that even the same mutation in the same gene may lead to distinct phenotypes.</p>

Detection of duplications or deletions of the PMP22 gene using real-time quantitative PCR / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect the duplication or deletion of peripheral myelin protein 22(PMP22) gene in Chinese patients with Charcot-Marie-Tooth disease(CMT) or hereditary neuropathy with liability to pressure palsies(HNPP) using real-time quantitative polymerase chain reaction.</p><p><b>METHODS</b>Duplications or deletions of PMP22 gene were detected in 113 CMT cases, 4 HNPP cases and 50 normal controls by using real-time quantitative PCR.</p><p><b>RESULTS</b>Thirty-six of 113 CMT cases had the PMP22 duplication, 4 HNPP cases had the PMP22 deletion. No duplication or deletion was found in 50 normal controls.</p><p><b>CONCLUSION</b>The PMP22 duplication rate in Chinese patients with CMT is 31.9%(36/113). PMP22 deletion is the common cause of HNPP.</p>

Protective effect of bFGF gene modified mesenchymal stem cells on cerebral ischemia in rats / 中华神经科杂志

Objective To investigate the protective effect of basic fibroblast growth factor(bFGF) gene modified mesenchymal stem cells(MSCs-bFGF)on cerebral isehemia in rats.Methods MSCs or MSCs-bFGF were transplanted into rat models of focal cerebral ischemia by intravenous injection.The neurological deficits and infarction volumes were evaluated,and the survival rate and differentiation of grafted MSCs were observed by double immunofiuoreseent labeling.Results In the rat cerebral ischemic model, both MSCs and MSCs-bFGF showed protective effect on the rats in comparison with control group.However, the protective effect was more significant in MSCs-bFGF group.Double immunofluorescent staining showed the number of BrdU-labeled and NeuN co-expression cells in MSCs-bFGF treated animals(127.40?7.43 and 11.20?3.09)were much more than in those of MSCs treated animals.While there was no significant difference between MSCs-bFGF and MSCs group in the number of GFAP co-expression cells.Conclusion MSCs transplantation has protective effect on cerebral ischemia in rats.Basic fibroblast growth factor gene modified MSCs is more effective than MSCs in neuroproteetion.