Novel androgen receptor gene variant containing a frameshift mutation in a patient with complete androgen insensitivity syndrome.

A variety of mutations in the androgen receptor (AR) gene are linked to androgen insensitivity syndrome (AIS). AIS is the most common specific cause of 46, XY disorder in sex development. Here, we reported a patient which presented as a female with 46, XY karyotype and normal female external genitalia. The patient was diagnosed with complete AIS caused by a novel mutation (NM_000044, c.2678-2726del, p. Pro893Leufs*35) in the AR gene. Targeted exome sequencing was used to detect the patient's androgen receptor gene mutations. Sanger sequencing was used to validate the mutation. This study showed that a novel mutation of the AR gene can cause complete AIS; the study also broadened the AR mutation spectrum and indicated that targeted exome sequencing could help facilitate the diagnosis of complicated disorders in sexual development.

The updated beta-spectrin mutations in patients with hereditary spherocytosis by targeted next-generation sequencing.

Hereditary spherocytosis (HS) with hemolysis, splenomegaly, and jaundice as the main clinical symptoms varied in different population and SPTB mutated rate is common except for ANK1 in the Chinese population, whereas only a few studies have been reported. Here, 11 Chinese pediatric patients with newly SPTB mutations detected by targeted next generation sequencing technology were included and analyzed in our study. The characteristics of mutation separation were verified among family members by bidirectional Sanger sequencing. The detected 11 mutations were novel, all of which were heterozygotes, including five de novo mutations, five maternal mutations, and one paternal mutation. Meanwhile, the 11 different novel mutation sites distributed on and near the seven exons included four pathogenic sites and seven likely pathogenic sites. The detection of 11 novel mutation sites gene expanded the mutant spectrum of the SPTB gene, and provided corresponding clinical data, which laid a foundation for the subsequent studies on HS in Chinese population, especially in pediatric patients.

The repertoire features of T cell receptor ß-chain of different age and gender groups in healthy Chinese individuals.

T cell immunity is dependent on T cell receptor (TCR) recognition of large numbers of antigenic peptides presented in the context of major histocompatibility complex (MHC) class I and II molecules. To explore whether the TCR ß-chain repertoire changes with different ages and genders in healthy Chinese individuals, we analyzed the TCR ß-chain repertoire in 154 healthy Chinese individuals by High-throughput sequencing (HTS) with age (age range: 6-70) and each age group contains about 20 individuals (male and female). Here we report that the extent of TCR diversity was not dependent on gender but it was significantly different between age groups. We found that the rearrangement of the V with J genes in T cell receptor ß-chain was highest at the age of 21-30. Moreover, we found that the combination of V6-1 and J2-1 gene had the highest expression over a human lifespan. We further identified J2-1 and V7-2 gene expressed higher at the age of 6-10 and 11-20 than other age groups. However, D gene in TCR ß-chain was not significantly diverse in different age groups. In addition, the T cell receptor ß complementarity-determining region 3 (CDR3) amino acid sequence expressed the highest between the age of 21-30. These results showed different features of TCR ß-chain repertoire in different groups of healthy Chinese individuals. In conclusion, it was expected that these TCR repertoires could serve as a useful tool for investigating the role of immune profiling in healthy Chinese individuals. These results stress the importance of considering age as a factor for immune response.

The RLA1/SMOS1 Transcription Factor Functions with OsBZR1 to Regulate Brassinosteroid Signaling and Rice Architecture.

Brassinosteroids (BRs) are plant-specific steroid hormones that control plant growth and development. Recent studies have identified key components of the BR signaling pathway in Arabidopsis thaliana and in rice (Oryza sativa); however, the mechanism of BR signaling in rice, especially downstream of GSK3/SHAGGY-like kinase (GSK2), remains unclear. Here, we identified a BR-insensitive rice mutant, reduced leaf angle1 (rla1), and cloned the corresponding gene. RLA1 was identical to the previously reported SMALL ORGAN SIZE1 (SMOS1), which was cloned from another allele. RLA1/SMOS1 encodes a transcription factor with an APETALA2 DNA binding domain. Genetic analysis indicated that RLA1/SMOS1 functions as a positive regulator in the BR signaling pathway and is required for the function of BRASSINAZOLE-RESISTANT1 (OsBZR1). In addition, RLA1/SMOS1 can interact with OsBZR1 to enhance its transcriptional activity. GSK2 can interact with and phosphorylate RLA1/SMOS1 to reduce its stability. These results demonstrate that RLA1/SMOS1 acts as an integrator of the transcriptional complex directly downstream of GSK2 and plays an essential role in BR signaling and plant development in rice.

Histone deacetylase HDA6 enhances brassinosteroid signaling by inhibiting the BIN2 kinase.

Glycogen synthase kinase 3 (GSK3)-like kinases play important roles in brassinosteroid (BR), abscisic acid, and auxin signaling to regulate many aspects of plant development and stress responses. The Arabidopsis thaliana GSK3-like kinase BR-INSENSITIVE 2 (BIN2) acts as a key negative regulator in the BR signaling pathway, but the mechanisms regulating BIN2 function remain unclear. Here we report that the histone deacetylase HDA6 can interact with and deacetylate BIN2 to repress its kinase activity. The hda6 mutant showed a BR-repressed phenotype in the dark and was less sensitive to BR biosynthesis inhibitors. Genetic analysis indicated that HDA6 regulates BR signaling through BIN2. Furthermore, we identified K189 of BIN2 as an acetylated site, which can be deacetylated by HDA6 to influence BIN2 activity. Glucose can affect the acetylation level of BIN2 in plants, indicating a connection to cellular energy status. These findings provide significant insights into the regulation of GSK3-like kinases in plant growth and development.

Brassinosteroid signaling regulates leaf erectness in Oryza sativa via the control of a specific U-type cyclin and cell proliferation.

Leaf erectness is key in determining plant architecture and yield, particularly in cereal crops. Brassinosteroids (BRs) play a unique role in controlling this trait in monocots, but the underlying cellular and molecular mechanisms remain big mysteries. Here we report that the abaxial sclerenchyma cell number of rice lamina joints (LJs) is closely related to leaf erectness, and BR signaling tightly regulates their proliferation. We identified a rice U-type cyclin CYC U4;1 enriched in rice LJs, with its expression accompanying LJ development. Genetic and biochemical studies demonstrated that CYC U4;1 plays a positive role in promoting leaf erectness by controlling the abaxial sclerenchyma cell proliferation. Furthermore, BR signaling inhibits the abaxial sclerenchyma cell division by coordinately regulating CYC U4;1 expression through BES1 and CYC U4;1 protein activity through GSK3 kinases. These results support a key role of the cyclin CYC U4;1 in mediating BR-regulated cell division to control leaf erectness.