Background Polyglucosan body myopathy 1 (PGBM1) is a type of glycogen storage disease that can cause skeletal muscle myopathy and cardiomyopathy with or without immunodeficiency due to a pathogenic mutation in the RBCK1 gene. PGBM1 has been reported in only 14 European and American families, and no cognitive impairment phenotype was reported. Its prevalence in Asia is unknown. Case presentation: We report a Chinese boy with teenage onset of skeletal muscle myopathy and mild cognitive impairment. Whole-exome sequencing analysis identified a homozygous missense mutation in RBCK1 (c.1411G > A:p.Glu471Lys). A muscle biopsy indicated the accumulation of periodic acid-Schiff-positive material, which could be ubiquitinated by immunohistochemistry with an anti-ubiquitin antibody. In skeletal muscle tissue, HOIL-1 and HOIP protein levels were lower than those in the control, confirming the phenotype of an RBCK1 mutation. MRI revealed abnormal cerebral white matter signals. Immune system and cardiac examination found no abnormalities. The patient was diagnosed with PGBM1 with no effective treatment. Conclusions This case from China with a novel homozygous missense mutation in RBCK1 extends the phenotypic spectrum and geographical distribution of PGBM 1, which may cause cerebral white matter changes and cognitive impairment.

BackgroundHepatitis B virus (HBV) genotypes show genomic variations, resulting in different CpG islands in each HBV genotypes or subgenotype. This study aimed to establish reference sequences for each HBV subgenotype of A–H genotypes and to analyze the characteristics of the CpG islands.Material/MethodsThere were 3,037 retrieved whole-genome sequences of HBV genotypes A–H from GenBank, 28 subgenotype reference sequences were established for these genotypes. CpG islands of the subgenotype reference sequences were analyzed, and 939 strains were selected from the 3,037 genomic sequences. Differences in CpG islands between subgenotypes were compared using the chi-squared and non-parametric tests.ResultsOf the 28 subgenotype reference sequences established, 11 subgenotype reference sequences lacked CpG island I, and only F4 contained a new CpG island. Of all selected strains, 48.35% (454/939) contained three traditional CpG islands I, II, and III (no new islands); 45.05% (423/939) lacked CpG island I; 38.98% (366/939) contained only CpG islands II and III; and 12.46% (117/939) contained new islands (genotypes A1, D7) (genotype G had no new islands). Strains with or without CpG island I, or new islands between subgenotypes of each HBV genotype were significantly different (P<0.05). Strains containing CpG islands I, II, and III and new islands among different subtypes in HBV genotypes A, C, and F were significantly different (P<0.05).ConclusionsDifferent HBV genotypes and subgenotypes had characteristic CpG island patterns. Strains with or without CpG island I, or new islands among subgenotypes of each HBV genotype, were significantly different.

Background and Aim. Significantly reduced serum ceruloplasmin (Cp) is the most important clue in the diagnosis of Wilson’s disease (WD) and is well known to clinicians. The false increase in Cp in some WD patients, which overlaps with that in non-WD liver disease patients, decreases the diagnostic accuracy. The aims of our study were to understand the factors associated with Cp normalisation in WD patients and identify these WD patients using usual predictors. Methods. We retrospectively screened individuals with serum Cp ≥ 140 mg/L from 1032 WD patients who were hospitalised for the first time. Logistic regression analyses were performed in a case-control study between the WD cohort and another liver disease cohort to explore the independent risk factors for WD diagnosis and establish a regression model to identify them. The follow-up medical records of the WD cohort were subjected to mixed-effects model analysis in a longitudinal study to discover factors associated with Cp normalisation. Results. Eighty-six WD patients and their 353 medical records and another 98 non-WD liver disease patients were included in the present study. Cp normalisation was significantly associated with the copper burden and liver function indexes, such as urinary copper, γ-glutamyltransferase, and albumin ( p ≤ 0.001 ). Logistic regression analysis showed that age and serum creatinine ( p ≤ 0.001 ) were independent risk factors associated with WD. The AUC value of the regression model in the total cohort was 0.926 ( p ≤ 0.001 ). At a cutoff value of ≥0.617 and ≥−1, the positive and negative predictive values were both 90.8% for WD. Conclusion. Increased serum Cp in WD patients is related to excessive copper burden and hepatic injury, and common tests can effectively distinguish WD patients from other liver injury patients.