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Objective:To discuss the clinical characteristics of autosomal recessive spinocerebellar ataxia type 16 patients caused by STUB1 gene mutation, in order to improve the clinical doctors′ understanding of the disease. Methods:The clinical manifestations, auxiliary examinations and genetic testing of 1 autosomal recessive spinocerebellar ataxia type 16 patient caused by STUB1 gene variants diagnosed in Qilu Hospital of Shandong University in May 2022 were collected, and the relevant literature was reviewed to summarize the clinical and genetic characteristics of this type of disease. Results:The proband was a 35-year-old male presenting with unsteady walk and dysarthria. Magnetic resonance imaging showed cerebellar atrophy. Next generation sequencing revealed compound heterozygous c.322dupG (p.Glu108Glyfs *4) and c.433A>C (p.Lys145Gln) variants in the STUB1 gene (according to the transcript NM_005861.4), and the c.322dupG (p.Glu108Glyfs *4) variant was a novel variant. Pedigree verification revealed the 2 variants were respectively inherited from the proband′s healthy parents. A total of 12 foreign literatures reported 32 autosomal recessive spinocerebellar ataxia type 16 patients. The main clinical manifestations were ataxia, dysarthria and tendon hyperreflexia. Besides, nystagmus, spasticity, action tremors, and myoclonus can be present. Magnetic resonance imaging predominantly showed cerebellar atrophy. Conclusions:The patient with autosomal recessive spinocerebellar ataxia type 16 caused by STUB1 gene variant is rare in China. The main clinical manifestation is cerebellar ataxia, and brain imaging reveals remarkable cerebellar atrophy. Genetic testing is helpful for definite diagnosis.
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Objective:To investigate the clinical, pathological and genetic features of 3 cases of limb-girdle muscular dystrophy 2A (LGMD2A) caused by non-canonical splice site mutations in the CAPN3 gene. Methods:For the 3 LGMD2A patients admitted to Qilu Hospital of Shandong University from July 2016 to July 2018 were selected as the subjects. Clinical data were collected, whole exome sequencing was conducted, and the candidate variants were verified by Sanger sequencing. Total RNA was extracted from the skeletal muscle tissue of 3 probands and effects of splicing mutations on pre-mRNA splicing in the CAPN3 gene were verified by reverse-transcription polymerase chain reaction. Total protein was extracted from the muscle tissue of the probands and expression level of calpain 3 protein was detected by Western blotting. Results:All the 3 probands presented muscle weakness in upper and lower limbs, and muscle weakness in proximal limbs was more severe. Muscle biopsies all indicated myogenic impairment. Genetic sequencing showed proband 1 carried compound heterozygous c.2185-14T>G and c.2305C>T (p.R769W) mutations in the CAPN3 gene, proband 2 carried compound heterozygous c.1193+30G>A and c.2069_2070delAC (p.H690Rfs *9) mutations, and proband 3 carried homozygous c.1194-9A>G mutations in the CAPN3 gene. Splicing assay showed the c.2185-14T>G mutation located in intron 20 induced retention of the entire intron 20, the c.1193+30G>A mutation in intron 9 induced retention of the first 31 nucleotides of intron 9, and the c.1194-9A>G mutation in intron 9 induced retention of the last eight nucleotides of intron 9. Western blotting revealed deficiency of calpain 3 protein in skeletal muscle of proband 1 and proband 2. Conclusions:The clinical manifestation of LGMD2A is muscle weakness predominantly in proximal limbs, and the muscle pathology is mostly characterized by myogenic impairment.Moreover, aberrant splicing of pre-mRNA caused by non-canonical splice site mutations plays a pathogenic role in this disease.
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OBJECTIVE@#To investigate the early effectiveness of transiliac-transsacral screws internal fixation assisted by augmented reality navigation system HoloSight (hereinafter referred to as "computer navigation system") in the treatment of posterior pelvic ring injuries.@*METHODS@#A retrospective analysis was made in the 41 patients with posterior pelvic ring injuries who had been treated surgically with transiliac-transsacral screws between June 2022 and June 2023. The patients were divided into navigation group (18 cases, using computer navigation system to assist screw implantation) and freehand group (23 cases, using C-arm X-ray fluoroscopy to guide screw implantation) according to the different methods of transiliac-transsacral screws placement. There was no significant difference in gender, age, body mass index, causes of injuries, Tile classification of pelvic fracture, days from injury to operation, usage of unlocking closed reduction technique between the two groups ( P>0.05). The time of screw implantation, the fluoroscopy times, the guide wire adjustment times of each screw, and the incidence of complications were recorded and compared between the two groups. The position of the transiliac-transsacral screw was scanned by CT within 2 days after operation, and the position of the screw was classified according to Gras standard.@*RESULTS@#The operation was successfully completed in both groups. The time of screw implantation, the fluoroscopy times, and the guide wire adjustment times of each screw in the navigation group were significantly less than those in the freehand group ( P<0.05). There were 2 cases of incision infection in the freehand group, and the incision healed by first intention after active dressing change; there was no screw-related complication in the navigation group during operation and early period after operation; the difference in incidence of complications between the two groups (8.7% vs. 0) was not significant ( P=0.495). According to the Gras standard, the screw position of the navigation group was significantly better than that of the freehand group ( P<0.05).@*CONCLUSION@#Compared with the traditional freehand method, the computer navigation system assisted transiliac-transsacral screws internal fixation in the treatment of posterior pelvic ring injuries has advantages of improving the accuracy of screw implantation and reducing radiation damage and the time of screw implantation.