A case report of peroneal muscle atrophy type 2A2 with central nervous system involvement as initial presentation.

BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a group of single-gene hereditary diseases of peripheral nerve with high clinical variability and genetic heterogeneity. The typical clinical manifestations include progressive muscle weakness and muscle atrophy in the distal extremities, accompanied by disappearance of tendon reflexes and distal sensory disturbances. CMT2A2 (OMIM: 609260) is caused by the mutation of MFN2 (OMIM: 608507), is the most common type of axonal pattern. Although a small number of patients with X-linked CMT1 (CMT1X) present with central nervous system involvement, including reversible white matter lesions, it is rarely in CMT2A2. CASE PRESENTATION: A 3-year and 5-month-old girl had experienced motor lag, muscle tension, and abnormal gait for over a year. A reexamination of cranial MRI revealed an anterior enlargement of the abnormal signal range in the lateral ventricles and bilateral frontal lobes. And the whole exon sequencing showed that this girl carried a heterozygous missense mutation c.314C > T of MNF2 gene, inherited from her mother. CONCLUSIONS: In this study, we retrospectively analyzed the clinical and molecular genetic findings of a child with Charcot-Marie-Tooth disease A2 with central nervous system involvement as the initial presentation, and explored its pathogenic mechanism.

Case report: Novel compound heterozygous missense mutations in the DDHD2 gene in a Chinese patient associated with spastic paraplegia type 54.

Background: Spastic paraplegia type 54 (SPG54) is a rare inherited autosomal recessive disorder, and a complex hereditary spastic paraplegia (HSP) caused by mutations in the phospholipase DDHD2 gene. SPG54 is characterized by early onset of spastic paraplegia, intellectual disability and dysplasia of corpus callosum. Case presentation: We report a 9 years and 5 months old Chinese girl with progressive spasm of the lower limbs, muscle weakness and intellectual disability. Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia and thinning of the corpus callosum. According to the Wechsler Intelligence Scale, her IQ is 42. By whole exome sequencing, novel compound heterozygous missense mutations in the DDHD2 gene [c.168G>C, p.(Trp56Cys) and c.1505T>C, p.(Phe502Ser)] were identified in the proband. Comparative amino acid sequence alignment across different species revealed that Trp56 and Phe502 in the DDHD2 protein were highly conserved during evolution. And multiple in silico prediction tools suggested that both mutations were deleterious. Conclusions: Our study reports a very rare case of complicated HSP caused by two novel compound heterozygous mutations in the DDHD2 gene. Our findings expand the genetic spectrum of SPG54.

Novel CLCN4 variant associated with syndromic X-linked intellectual disability in a Chinese girl: a case report.

BACKGROUND: The Raynaud-Claes type of X-linked syndromic mental retardation (MRXSRC) is a very rare condition, by intellectual disability ranged from borderline to profound, impaired language development, brain abnormalities, facial dysmorphisms and seizures. MRXSRC is caused by variants in CLCN4 which encodes the 2Cl-/H+ exchanger ClC-4 prominently expressed in brain. CASE PRESENTATION: We present a 3-year-old Chinese girl with intellectual disability, dysmorphic features, brain abnormalities, significant language impairment and autistic features. Brain magnetic resonance imaging (MRI) showed a thin corpus callosum, a mega cisterna magna and ventriculomegaly. Whole exome sequencing (WES) was performed to detect the molecular basis of the disease. It was confirmed that this girl carried a novel heterozygous missense variant (c.1343C > T, p.Ala448Val) of CLCN4 gene, inherited from her mother. This variant has not been registered in public databases and was predicted to be pathogenic by multiple in silico prediction tools. CONCLUSION: Our investigation expands the phenotype spectrum for CLCN4 variants with syndromic X-linked intellectual disability, which help to improve the understanding of CLCN4-related intellectual disability and will help in genetic counselling for this family.

A de novo 10q11.23q22.1 deletion detected by whole genome mate-pair sequencing: a case report.

BACKGROUND: Interstitial deletions of chromosome band 10q11-q22 was a genomic disorder distinguished by developmental delay, congenital cleft palate and muscular hypotonia. The phenotypes involved were heterogeneous, hinge on the variable breakpoints and size. CASE PRESENTATION: Here, we presented a patient with soft palate cleft, growth and development delay. The patient was a 2 years and 5 months girl who was not able to walk unless using a children's crutches to support herself. Whole-exome sequencing (WES) and whole-genome mate-pair sequencing (WGMS) were both performed by next generation sequencing (NGS). A 20.76 Mb deletion at 10q11.23q22.1 (seq[GRCh37/hg19]del(10)(50,319,387-71,083,899) × 1) was revealed by the WGMS, which was verified as de novo by quantitative polymerase chain reaction (QPCR). CONCLUSION: Children with 10q11-q22 deletions greater than 20 MB have never been reported before, and we are the first to report and provide a detailed clinical phenotype, which brings further knowledge of 10q11-q22 deletions.

Circular RNA ZNF609 promotes the malignant progression of glioma by regulating miR-1224-3p/PLK1 signaling.

Objective: Previous studies have demonstrated that circular RNAs (circRNAs) play vital roles in pathological process of various diseases, including tumors. This study aimed at exploring the role and mechanism of circRNA RNA ZNF609 (circ-ZNF609) in the occurrence and development of glioma. Materials and methods: Real-time quantitative PCR (qRT-PCR) was applied to measure the expression of circ-ZNF609, miRNA-1224-3p (miR-1224-3p) and Polo-like kinase 1 (PLK1) in glioma tissues and cell lines. Furthermore, the association between circ-ZNF609 and clinical features of glioma was analyzed. CCK8 assay, EdU assay and Transwell assay were conducted to detect the effect of circ-ZNF609, miR-1224-3p and PLK1 on proliferation, migration and invasion in glioma cells. Then, we investigated the underlying mechanism of circ-ZNF609 by bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation (RIP), qRT-PCR and western blotting assay. Results: Circ-ZNF609 was confirmed prominently upregulated in glioma. Inhibition of circ-ZNF609 could obviously suppress glioma cell proliferation, migration and invasion, while overexpression of circ-ZNF609 promoted glioma growth and metastasis. In vivo, xenotransplanted tumor model also showed that overexpression of circ-ZNF609 could promote in vivo glioma growth. Mechanistically, circ-ZNF609 could promote PLK1 expression via binding to miR-1224-3p, circ-ZNF609/miR-1224-3p/PLK1 was shown responsible for circ-ZNF609 promoting glioma growth and metastasis. Conclusion: Together, our results revealed that circ-ZNF609 elevates glioma growth and metastasis via enforcing PLK1 expression by competitively binding miR-1224-3p, suggesting that circ-ZNF609 might be an underlying therapeutic target for glioma.

Evaluation of stress and pain in young children with cerebral palsy during early developmental intervention programs: a descriptive study.

OBJECTIVE: The aim of this study was to use the Face, Legs, Activity, Cry, Consolability Scale; salivary cortisol levels; and withdrawal reflex thresholds to assess pain, stress, and pain sensitivity in young children with cerebral palsy during early developmental intervention programs. DESIGN: A total of 40 children with cerebral palsy (age range, 1-4 yrs) participated in the early intervention programs, which included neurodevelopmental treatment, neuromuscular electrical stimulation, occupational therapy, head acupuncture, and Chinese traditional manipulation five times per week for 3 wks. The Face, Legs, Activity, Cry, Consolability Scale was applied during the course of each treatment, and salivary cortisol samples were obtained from each child 10 mins before and 10 mins after each treatment. Withdrawal reflex thresholds were assessed via mechanical stimulation of the foot with von Frey hairs. RESULTS: All treatment programs caused some degree of pain. In descending order, the extents of the pain caused by each treatment were head acupuncture, neurodevelopmental treatment, neuromuscular electrical stimulation, Chinese traditional manipulation, and occupational therapy. There were statistically significant increases in salivary cortisol levels after the head acupuncture (P < 0.001), neurodevelopmental treatment (P < 0.001), neuromuscular electrical stimulation (P < 0.001), and Chinese traditional manipulation (P < 0.001) treatments. No significant changes were found in the withdrawal reflex thresholds during the study (P > 0.05). CONCLUSIONS: The results of this study demonstrate that early developmental intervention programs cause pain and stress in young children with cerebral palsy.

Day vs. day-night use of ankle-foot orthoses in young children with spastic diplegia: a randomized controlled study.

OBJECTIVE: The aim of this study was to compare the effectiveness of treatment with hinged ankle-foot orthoses (AFOs) during the day vs. during both the day and the night in young ambulant children with spastic diplegia. DESIGN: In this prospective randomized controlled trial, 112 ambulatory children (70 boys and 42 girls; mean age, 2 yrs 6.93 mos; range, 1 yr 1 mo to 4 yrs 0 mo) with spastic diplegia participated. Forty-eight were classified at level I of the Gross Motor Function Classification System; the remaining 64 were at level II. Using stratified randomization, all children were assigned to either the day AFO-wearing group (n = 56, wearing AFOs all day) or the day-night AFO-wearing group (n = 56, wearing AFOs all day and all night). The two groups underwent conventional rehabilitative treatments five times a week for 8 wks. The primary outcomes measured were passive ankle dorsiflexion angle and sections D and E of the 66-item Gross Motor Function Measure; the root mean square of surface electromyography in the ventral and dorsal lower limb muscles was compared in a subgroup (ten from each group). RESULTS: Seven children did not complete the full intervention: three in the day AFO-wearing group and four in the day-night AFO-wearing group. Significant baseline-postintervention improvements were found for passive ankle dorsiflexion angle and the 66-item Gross Motor Function Measure in both groups (P < 0.05). On the basis of the score changes, there was no significant difference between these two groups with respect to passive ankle dorsiflexion angle; however, the improvements in the 66-item Gross Motor Function Measure were significantly better in the day AFO-wearing group (P < 0.01). A significant root mean square decrease in gastrocnemius (P < 0.05) was present after the intervention in the day AFO-wearing group, whereas the muscles affected in the day-night AFO-wearing group were the gastrocnemius (P < 0.05) and the tibialis anterior (P < 0.001). CONCLUSIONS: The results demonstrate that the daytime use of AFOs was more effective in improving Gross Motor Function Measure scores than the day-night use. In addition, the prolonged wearing of AFOs may influence muscle activity, which should be monitored in the clinic.