The current study updated data on the incidence and prevalence of 121 rare diseases listed in China's First List of Rare Diseases to provide rationales and references for the development and promotion of rare-disease-related policies. The National Health Commission of the People's Republic of China issued the Rare Disease Diagnosis and Treatment Guide (2019) (denoted here as China's Rare Disease Diagnosis and Treatment Guide). Then 121 diseases were registered with the national rare disease diagnosis and treatment network. The incidence/prevalence of 121 rare diseases varied from country to country. Data are available for a total of 76 rare diseases (76 of 121 rare diseases, 62.81%) in China, including data on the incidence of 23 rare diseases (19.01%) and data on the prevalence of 66 (54.55%). There are data on the incidence/prevalence of 112 rare diseases (112 of 121 rare diseases, 92.56%) at the global level, including data on the incidence of 86 rare diseases (71.07%) and data on the prevalence of 91 (75.21%). On average, the incidence of progressive muscular dystrophies, hyperphenylalaninemia, citrullinemia, and methylmalonic acidemia is over 1/10,000 in China. The prevalence of coronary artery ectasia, congenital scoliosis, retinitis pigmentosa, severe congenital neutropenia, congenital hyperinsulinemic hypoglycemia, and osteogenesis imperfecta is over 1/10,000 in China. All of these figures are beyond the cut-off of 1/10,000 according to the 2021 definition of rare diseases in China. As registration and investigation of rare diseases continues, the spectrum of rare diseases in some provinces is expanding. Diseases such as idiopathic pulmonary arterial hypertension, hepatolenticular degeneration, hemophilia, amyotrophic lateral sclerosis, idiopathic pulmonary fibrosis, and multiple sclerosis are relatively prevalent in some regions and cities of China. Registration efforts promote the correction of incidence/prevalence data, development of orphan drugs, coverage by medical insurance, and development of clinical and diagnostic pathways.

This meta-analysis compared the clinical outcomes between two alternative surgeries for patients with cervical spondylosis, namely anterior cervical discectomy and fusion (ACDF) without plate (ACDFWP) vs. anterior cervical disc arthroplasty (ACDA). We searched databases, including PubMed, EMBASE, Cochrane Library, Google Scholar, and Web of Science (firstly available-2019). A standard meta-analysis was performed with the included studies. A Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool was used for the evaluation of the study quality of nonrandomized-controlled trials (nRCTs), while a Risk of Bias (RoB) battery was used for randomized controlled trials (RCTs). Eight studies involving 640 patients were included. No significant difference was found in the indices of Neck Disability Index (NDI) score, Visual Analog Score (VAS), Japanese Orthopaedic Association (JOA) score, operative time, blood loss, Swallowing Quality of Life Score (SWAL-QL), and complications. Cervical alignment was significantly better in the ACDFWP than in ACDA (mean difference (MD) = −0.67, 95% confidence interval (CI) [−1.11, −0.23], P = 0.003, I² = 20%). Although the alternative ACDFWP was slightly superior in terms of the index of cervical alignment, the limited research on this subject present insufficient evidence. Further well-designed studies are warranted in the future.

Smooth muscle disorders affecting both the intestine and the bladder have been known for a decade. However, the recent discovery of genes associated with these dysfunctions has led to the description of several clinical phenotypes. We performed a systematic review of all published cases involving seven genes with pathogenic variants, ACTG2, MYH11, FLNA, MYLK, RAD21, MYL9 and LMOD1, and included 28 articles describing 112 patients and 5 pregnancies terminated before birth. The most commonly described mutations involved ACTG2 (75/112, 67% of patients), MYH11 (14%) and FLNA (13%). Twenty-seven patients (28%) died at a median age of 14.5 months. Among the 76 patients for whom this information was available, 10 (13%) had isolated chronic intestinal pseudo-obstruction (CIPO), 17 (22%) had isolated megacystis, and 48 (63%) had combined CIPO and megacystis. The respective proportions of these phenotypes were 9%, 20% and 71% among the 56 patients with ACTG2 mutations, 20%, 20% and 60% among the 10 patients with MYH11 mutations and 50%, 50% and 0% among the 7 patients with FLNA mutations.

The guidelines provided by American College of Medical Genetics and Genomics (ACMG) and the Association of Molecular Pathology (AMP) (ACMG/AMP guidelines) suggest a framework for the classification of clinical variants. However, the interpretations can be inconsistent, with each definition sometimes proving to be ambiguous. In particular, there can be difficulty with interpretation of variants related to the X-linked recessive trait. To confirm whether there are biases in the interpretation of inherited traits, we reanalyzed variants reported prior to the release of the ACMG/AMP guidelines. As expected, the interpretation ratio as pathogenic or likely pathogenic was significantly lower for variants related to the X-linked recessive trait. Evaluation of variants related to the X-linked recessive trait, hence, need to consider whether the variant is identified only in males in accordance with the X-linked recessive trait. The ACMG/AMP guidelines should be revised to eliminate the bias revealed in this study.

Healthcare providers play an important role in improving the health of Inborn Error of Metabolism (IEM) patients. However, IEM knowledge level among local healthcare students has yet to be determined. Thus, the aim of this study is to assess the knowledge and perception of IEM among local healthcare students. An online self-administered questionnaire was distributed to 378 students across the Faculty of Health Science, Pharmacy and Dentistry from a selected public university in Lembah Klang, Malaysia. For knowledge, a score of 1 is assigned to each correct answer with a maximum total score of 14. Likert scale was used to determine their perception of IEM. The total mean score of IEM knowledge among healthcare students is 5.8. There was no significant difference of mean score of IEM knowledge among the students from the Faculty of Health Science (6.1 ± 2.7), Pharmacy (5.5 ± 2.6) and Dentistry (5.8 ± 2.8). However, the score of knowledge is observed to be significantly different by ethnicity, religion and family history of IEM (p < 0.05). Furthermore, students with experience of meeting an IEM patient and attending IEM classes scored higher than those with no experience (p < 0.05). Most of the healthcare students (89.5%) perceived their knowledge to be insufficient and very poor. Majority of the students from faculty of pharmacy (70.8%) agreed that the IEM course should be mandatory compared to health sciences and dentistry (p < 0.05). This study identified an overall inadequacy of knowledge of IEM among healthcare students. There is a pressing need to improve the IEM-related knowledge and awareness of Malaysian healthcare students. This can be accomplished by incorporating online classes that emphasizes the treatment and management of IEMs in the university curriculum.

Pediatric adrenocortical carcinomas (ACC) are rare aggressive neoplasms with heterogeneous prognosis, and often produce a most lethal malignant tumor, whereas its aetiology is still unclear. The aim of the present study was to identify the factors responsible for the development of pediatric ACC, a better understanding of the disease, and investigate new molecular biomarkers and therapeutic targets. To identify the key genes and miRNAs linked to pediatric ACC, as well as their potential molecular mechanisms, the GSEGSE75415 and GSE169253 microarray datasets were analyzed. A total of 329 differentially produced genes (DEGs) and 187 differentially produced miRNAs (DEMs) were obtained after analyzing the GSEGSE75415 and GSE169253 datasets, respectively. Next, 3,359 genes were obtained by overlapping the target mRNAs of DEMs. Following protein-protein interaction network and Gene Ontology analysis, the ten nodes with the highest degrees were screened as hub genes. Among them, the highly expressed hub genes, MAPK1 and EP300, were associated with a worse overall survival. Additionally, hsa-miR-376, hsa-miR-148, hsa-miR-139, and hsa-miR-1305 were strongly associated with poorer survival. We proposed that the hub genes (MAPK1, EP300, hsa-miR-376, hsa-miR-148, hsa-miR-139, and hsa-miR-1305) may have a definite impact on cellular proliferation and migration in adrenocortical tumors. The roles of these hub genes in adrenocortical tumors may provide novel insight to improve the diagnosis and treatment of patients with pediatric ACC.

Interstitial microdeletions in the proximal region of the long arm of chromosome 6 are rare. Herein we have reported 12 patients with developmental delays associated with interstitial microdeletions in 6q ranging from q12 to q22. The microdeletions were detected by chromosomal microarray testing. To confirm the clinical significance of these deletions, genotype-phenotype correlation analysis was performed using genetic and predicted loss-of-function data. SIM1 was recognized as the gene responsible for developmental delay, particularly in Prader-Willi syndrome-like phenotypes. Other genes possibly related to developmental delay were ZNF292, PHIP, KCNQ5, and NUS1. To further establish the correlation between the genotype and phenotype, more patient information is required.

LUCA, the last universal common ancestor, is the hypothetical most recent common ancestor of the three domains of life which share the universal genes (UG). It seems interesting to evaluate whether the UG phylogeny has had an impact on current Human gene constraints. A list of human homologs of UG was retrieved from the eggNOG database. We analyzed this LUCA gene (LG) group, and a random sample of 500 genes from the gnomAD database (RG group). Gene constraint metrics were retrieved from gnomAD and associations with Mendelian diseases and modes of inheritance were retrieved from OMIM. The LG group consisted of 277 genes and the RG group, 492 (8 genes were in LG group). 38.6% of the genes in the LG group and 25.2% of the genes in the RG group were associated with a Mendelian disease (p < 0.0001). The mode of inheritance was more often autosomal recessive (69.0 vs. 50.5%), and less often autosomal dominant (19.0 vs. 31.3%), or mixed (6.0 vs. 12.1%) for those associated with the LG group (p = 0.048). The LG group was significantly more constrained for missense variants (MOEUF, 0.919 vs. 0.997, p < 0.0001) and was borderline significantly more constrained for loss-of-function variants (LOEUF, 0.872 vs. 0.947, p = 0.051). These results suggest that the UG in humans differs from the rest of the genome in terms of constraints and associated Mendelian diseases. It suggests that phylogenic data can explain some of the characteristics of human genes and could help in interpreting variants.

Since April 5, 2022, an increase in cases of severe acute hepatitis of unknown etiology among children with no underlying conditions was first reported in the United Kingdom (UK). Testing excluded viral hepatitis types A, B, C, D, and E and other known common and uncommon infectious and non-infectious causes of acute hepatitis. As of May 26, 2022, 650 cases of acute hepatitis of unknown etiology in children have been reported in at least 33 countries worldwide, with 99 additional cases pending classification. Here, the current prevalence of this condition around the world, a hazard analysis, possible causes, the risk of an outbreak in China, and advice on prevention have been briefly reviewed.

Cholangiocytic adenoma in the hilar bile duct is rare, and elevated IgG4 at the same time is extremely rare. This situation has not been reported in the literature. Nonetheless, the current case involved hilar biliary cystadenoma with elevated IgG4 levels. A 66-year-old man presented at this hospital with dark tea-colored urine. Preoperative imaging studies suggested hilar cholangiocarcinoma. This case demonstrates the difficulty of preoperative diagnosis of benign hilar lesions and the rarity of two combined benign lesions. A point of contention is whether this case should be treated with surgery or hormone therapy.