Genetic analysis of a child with Charlevoix-Saguenay spastic ataxia due to variant of SACS gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical feature and genetic variant of a child with autosomal recessive Charlevoix-Saguenay type spastic ataxia (ARSACS).@*METHODS@#Clinical data of a child who was admitted to the West China Second Hospital of Sichuan University on April 30, 2021 was collected. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).@*RESULTS@#The child, a 3-year-and-3-month-old female, had a complain of "walking instability for over a year". Physical and laboratory examination revealed progressive and aggravated gait instability, increased muscle tone of the right limbs, peripheral neuropathy of the lower limbs, and thickening of retinal nerve fiber layer. The results of WES revealed that she has harbored a maternally derived heterozygous deletion of exons 1 to 10 of the SACS gene, in addition with a de novo heterozygous c.3328dupA variant in exon 10 of the SACS gene. Based on the ACMG guidelines, the exons 1-10 deletion was rated as likely pathogenic (PVS1+PM2_Supporting), and the c.3328dupA was rated as a pathogenic variant (PVS1_Strong+PS2+PM2_Supporting). Neither variant was recorded in the human population databases.@*CONCLUSION@#The c.3328dupA variant and the deletion of exons 1-10 of the SACS gene probably underlay the ARSACS in this patient.

De novo variant of CSNK2B causes Poirier-Bienvenu neurodevelopmental syndrome: two case report / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical characteristics and CSNK2B gene variant of 2 children with Poirier-Bienvenu neurodevelopmental syndrome, and to identify the possible pathogenic causes and provide evidence for clinical diagnosis.@*METHODS@#Two children with Poirier-Bienvenu neurodevelopmental syndrome were selected from West China Second University Hospital, Sichuan University. The clinical manifestations, laboratory examination and CSNK2B gene variant were analyzed.@*RESULTS@#The main manifestations of 2 children were epilepsy, motor or intellectual retardation. Whole exon sequencing showed that CSNK2B gene c. 291+4A>T heterozygous splicing variant was found in case one, and CSNK2B copy number variation(CNV) was lost in case two. Case one received no special treatment, followed up for 8+ months, seizures and motor development were improved; case two had recurrent seizures for 9+ years, and received levetiracetam and clonazepam antiepileptic treatment. No seizures have occurred for 2 years now, and a large number of epileptic discharges can still be seen in video electroencephalogram (VEEG) with slightly backward intelligence and language development.@*CONCLUSION@#Our study further proves that the pathogenic variant of CSNK2B is related to epilepsy with developmental disorder, and enrich is the CSNK2B gene variant spectrum. The pathogenesis of CSNK2B has great clinical heterogeneity, with great difference in severity of nervous system injury and different prognosis, and agenesis of corpus callosum may be one of its clinical phenotypes.

Analysis of a case with Xia-Gibbs syndrome due to variant of AHDC1 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical and genetic characteristics of a child featuring Xia-Gibbs syndrome.@*METHODS@#Whole exome sequencing was carried out for the child.@*RESULTS@#The patient has presented with developmental delay, hypotonia, strabismus and snoring. Cranial MRI revealed hypomyelination, while the EEGs were normal. Genetic testing revealed a de novo variant of the AHDC1 gene, namely c.730delA (p.Ile244Serfs*16), which was classified as pathogenic (PVS1+PS2+PM2). Together with 60 cases from the literature, individuals harboring a AHDC1 variant commonly have delayed motor milestones, speech delay, facial dysmorphism and hypotonia. Dysgenesis of corpus callosum is also common. In total 47 AHDC1 variants have been reported, among which truncating variants were the most common type.@*CONCLUSION@#The c.730delA (p.Ile244Serfs*16) variant of the AHDC1 gene probably underlay the Xia-Gibbs syndrome in this patient. Above finding has provided a basis for the clinical diagnosis.

Analysis of clinical features and ZBTB18 gene variant in a child with autosomal dominant mental disorder type 22 / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical characteristics and ZBTB18 gene variant in a child with epilepsy and global developmental delay.@*METHODS@#Clinical data and laboratory examination of the patient were reviewed. Whole exome sequencing (WES) was also carried out for the family trio.@*RESULTS@#The main manifestations of the child included global developmental delay, short stature, epileptic seizures. EEG revealed frequent occurrence of sharp (slow) waves in the right central region during sleeping, with sharp waves occasionally seen in the frontal and right posterior temporal regions. Cranial MRI has shown no obvious abnormality. WES has identified a de novo pathogenic variant in the ZBTB18 gene [NM_205768.3: exon 2: c.1282_1283del (p.Phe428Leufs*72)]. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+PVS1_Moderate+PM2_Supporting). Following treatment with levetiracetam and rehabilitation, the seizures have been controlled for nearly half a year, with improvement of the psychomotor and language development. So far 28 children have been discovered with ZBTB18 gene mutations, and there was a significant difference in the clinical phenotypes of motor retardation, language retardation and epilepsy between those harboring frameshift/nonsense mutations and missense mutations.@*CONCLUSION@#The c.1282_1283del (p.Phe428leufs *72) variant of the ZBTB18 probably underlay the autosomal dominant mental disorder type 22 in this child. Compared with missense mutations, frameshift/nonsense mutations may predispose more to motor retardation, delayed language development and epilepsy.

Correlation between the residual amount of decellularization reagents in common tissue materials and cytotoxicity / 国际生物医学工程杂志

Objective:To study the correlation between the residual amounts of commonly used tissue decellularization reagents like sodium dodecyl sulfate (SDS), Triton X-100, sulfobetaine 10 (SB-10) and cytotoxicity, and to find the safety threshold for controlling the residual of the reagent.Methods:SDS, Triton X-100, SB-10 solutions of different concentrations were prepared, and the cytotoxicity of solutions of different concentrations was detected by L-929 cells and MC3T3-E1 cells according to the method of GB/T 16886.5. The mass concentration range of the above three decellularization reagents was refined, and the threshold for the residual non-cytotoxicity of a single reagent was determined. Mix the three reagents in pair or three blends, and determine the threshold of non-cytotoxicity after the reagents are mixed by cytotoxicity test.Results:SDS, Triton X-100 and SB-10 caused L-929 cells to produce cytotoxic concentration values of 4×10 -3, 2×10 -2 and 6×10 -1 mg/ml, and MC3T3-E1 cells 6×10 -3, 4×10 -2 and 2 mg/ml. The toxicity trend of the three reagents is SDS>Triton X-100>SB-10. When three reagents at critical concentrations are mixed in pairs or three, they have no cytotoxicity to L-929 cells and MC3T3-E1 cells. Conclusions:When using the above three decellularization reagents to prepare decellularized scaffolds, a variety of reagent cleaning procedures should be used to efficiently clean the tissues so that the residual amount of reagents is below the critical value to ensure the biological safety of the decellularized scaffolds.

Clinical and genetic analysis of PACS2 gene variant in two child patients with developmental and epileptic encephalopathy 66 / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotype and genetic characteristics of two children with developmental epileptic encephalopathy type 66.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the two children and their parents. Whole exome sequencing (WES) was carried out and suspected variant was verified by Sanger sequencing.@*RESULTS@#The main manifestations of the two children were neonatal onset seizures, hypotonia, global developmental delay, and facial dysmorphisms. Cranial MRI showed delayed myelination in case 1 and cerebellar dysgenesis in case 2. WES has identified a de novo pathogenic variant in the PACS2 gene in both patients, namely c.625G>A (p.Glu209Lys)(NM_001100913.3), which was reported as a pathogenic variant before. This variant was predicted to be pathogenic according to the American College of Medical Genetics and Genomics guideline (PS2+PM2+PP3). The seizures were controlled after combination treatment of sodium valproate and levetiracetam in both cases. At last follow-up, the motor and intellectual development of the 2 cases were improved. Compared with the cases reported, the clinical symptoms and signs of our cases were relatively mild, and the treatment effects were fairly good.@*CONCLUSION@#The variant of c.625G>A (p.Glu209Lys) in PACS2 gene is a hotspot variant of developmental epileptic encephalopathy 66. Gene testing can facilitate the clinical diagnosis and treatment.

Clinical experience of bladder muscle flap replacement for long segment defect of ureter in laparoscopic surgery / 中国内镜杂志

Objective To explore the effect of bladder muscle flaps for long segment defect of ureter middle-lower segment and reconstruction method in laparoscopic surgery. Methods Clinical data of 3 patients with long segment defect of ureter middle-lower segment, all of whom underwent laparoscopic surgery from May 2014 to April 2016 was retrospectively evaluated. There were 1 male and 2 females, in 2 cases with history of ureteroscopy holmium laser lithotripsy in ureter middle-lower segment, in 2 cases with history of repeated ESWL. Preoperative urinary tract ultrasound, CT and intravenous urography imaging showed severe hydronephrosis, ureter middle-upper segment severe hydroureter, ureter middle-lower segment severe stricture. Results Operations were successful in 3 cases. After reconstruction bladder muscle flaps average length of is 9.6 cm, The average operation time of 180 min, The average length of hospital stay for 10 d, Postoperative eighth weeks extracted the double J tube and used ureteroscopy showed anastomotic unobstructed, it may smooth Through 8.5 F ureteroscopy, and no infection and urinary leakage occurred, Follow-up ranged from 3 to 18 months. 3 cases hydronephrosis and hydroureter significantly reduce, ureter unobstructed, no narrow in ureter and muscle flap of tube joint, serum creatinine valueswere in normal range. Conclusions The bladder muscle flaps for the treatment of long segment defect of ureter middle-lower segment in laparoscopic surgery was a safe and effective therapy, but it must be accomplished by seasoned doctors.

Transurethral vaporization of the prostate using 1 470 nm diode laser in treatment of BPH / 中国内镜杂志

Objective To explore the efficacy and safety of Transurethral vaporization of the prostate using 1 470 nm diode laser in treatment of BPH.Methods 58 cases BPH patients underwent transurethral vaporization of the prostate using 1 470 nm diode laser from Dec. 2015 to Apr. 2016 were retrospectively analyzed, including the mean operation time and compared hemoglobin, electrolyte, urinary symptoms, before and after surgery.Result Operations were successfully performed in all the 58 cases, with average operation time of (48.2 ± 16.3) min. No difference was found in either hemoglobin decrease or electrolyte decrease before and after surgery. The patients were followed up for 1~3 months, which revealed a signiifcant reduction in IPSS and improvement in Qmaxand PVR (P < 0.05), compared with pre-operation. No severe complications were reported, including transurethral resection (TUR) syndrome, urinary incontinence and impaired erectile function.Conclusion Transurethral vaporization of the prostate using 1 470 nm diode laser is a safe and effective therapy for BPH. It has advantages of short learning curve, very little blood loss, high efifcacy. It has promising broad prospects.