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BackgroundSitosterolemia (STSL), also known as phytosterolemia, is a rare autosomal recessive hereditary disease caused by mutations in the ABCG5 or ABCG8 genes. The disease is a result of disorders in lipoprotein metabolism, and is characterized by tendinous and tuberous xanthomas, elevated plasma cholesterol and phytosterol levels, and thrombocytopenia and hemolytic anemia in several patients. The manifestations of STSL are diverse and can easily be misdiagnosed. In recent years, cases of this disease in children have been reported in succession. There is therefore a need for clinicians to improve identification of STSL and perform early intervention.MethodsWe evaluated four children with STSL caused by genetic mutations in ABCG5 or ABCG8, as well as their family members, by analyzing their clinical characteristics and performing Trio‐whole exome sequencing. The biological consequences of the mutations were analyzed using various bioinformatics software. We also analyzed the consequences of a mutation commonly observed in STSL patients on the structure of the protein involved.ResultsWe identified five previously unreported pathogenic mutations of different phenotypes of STSL: ABCG5 NM_022436:c.1337G>A; ABCG8 NM_022437:c.965‐1G>A, c.323‐1G>C, c.1418C>G and c.1534G>A. We also report the structural changes brought about by a mutation common in STSL patients, as well as the possible consequences of these changes.ConclusionsOur findings further broaden the genotypic and phenotypic profiles of the onset of STSL in the pediatric population and provide information for the diagnosis and treatment of this disease.

The biological role of RNA methylation in stem cells has attracted increasing attention. Recent studies have demonstrated that RNA methylation plays a crucial role in self-renewal, differentiation, and tumorigenicity of stem cells. In this review, we focus on the biological role of RNA methylation modifications including N6-methyladenosine, 5-methylcytosine, and uridylation in embryonic stem cells, adult stem cells, induced pluripotent stem cells, and cancer stem cells, so as to provide new insights into the potential innovative treatments of cancer or other complex diseases.

Background: Hypomagnesemia, seizures, and mental retardation (HSMR) syndrome is a rare genetic disease. Presently, only 24 cases have been reported and the clinical features of the disease are yet to be fully described, thereby making diagnosis challenging.Methods: Trio-whole-exome sequencing was used for the patient and her parents, and the structure of the variant protein was analyzed by molecular dynamics. Finally, the characteristics of HSMR were summarized by reviewing the previous literature. Results:The main disease manifestations in the patient were seizures, liver function damage, hypomagnesemia, atrial septal defect, and sinus arrhythmia.A novel mutation in CNNM2 (c.566A>G/p.Tyr189Cys) was identified by genetic detection. The parents were wild type, and the mutation was rated as pathogenic by American College of Medical Genetics and Genomics guidelines. Ab initio modeling and molecular dynamics simulation show that the mutation destroys the surrounding hydrogen bonds, which may reduce the local stability of the protein structure. In the previous literature, only 24 children with HSMR have been reported, mainly manifested as hypomagnesemia, mental retardation, seizures, and language and motor impairment. Conclusion:We have reported the second case of HSMR in the Chinese population, which further expands the phenotypic spectrum of congenital heart disease and the variation spectrum of CNNM2.

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Uniparental disomy (UPD) refers to a condition in which both homologous chromosomes have been inherited from one parent and can present as uniparental isodisomy (UPiD), uniparental heterodisomy UPD (UPhD), or as a mix of both (UPhD/UPiD). In the case of UPhD, two different homologous chromosomes from one parent are present; however, in the case of UPiD, two identical homologous chromosomes are inherited from one parent. The general mechanisms leading to UPD include nondisjunction in meiosis I and II resulting in trisomy and

We identified and characterized a Chinese family with autosomal dominant Brachydactyly type B1 (BDB1). Linkage analysis revealed that the disease gene of the Chinese BDB1 family was linked to ROR2 locus. Mutational hot spot of ROR2 gene was amplified by polymerase chain reaction (PCR) and sequenced directly. A c.2265C>A heterozygous mutation was detected in all of the patients. This mutation led to the change of p.Y755X in protein level and a truncated ROR2 protein losing integrant domains was generated. The mutation was detected in all the patients, but not in all the normal individuals of this family and 50 normal controls. This paper for the first time reported a c.2265C>A mutation in ROR2 gene of a family with BDB1 in China, which enriches ROR2 gene mutation spectrum in Chinese with BDB1.

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