[Clinical and genetic analysis of a child with Canavan disease due to compound heterozygous variants of ASPA gene].

OBJECTIVE: To analyze the clinical phenotype and genetic characteristics for a child with Canavan disease. METHODS: A child who was admitted to the Children's Hospital Affiliated to Shandong University on April 9, 2021 for inability to uphold his head for 2 months and increased muscle tone for one week was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing. RESULTS: Genetic testing revealed that the child has harbored compound heterozygous variants of the ASPA gene, including a paternally derived c.556_559dupGTTC (p. L187Rfs*5) and a maternally derived c.919delA (p. S307Vfs*24). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2_Supporting+PM3). CONCLUSION: The c.556_559dupGTTC (p.L187Rfs*5) and c.919delA (p.S307Vfs*24) compound heterozygous variants of the ASPA gene probably underlay the pathogenesis of Canavan disease in this child.

Ectopic overexpression of a cotton plastidial Na+ transporter GhBASS5 impairs salt tolerance in Arabidopsis via increasing Na+ loading and accumulation.

MAIN CONCLUSION: GhBASS5 is a member of the bile acid sodium symporter (BASS) gene family from cotton and a plastid-localized Na+ transporter that negatively regulates salt tolerance of plants. Soil salinization is a major constraint on global cotton production, and Na+ is the most dominant toxic ion in salinity stress. Hence, insights into the identities and properties of transporters that catalyze Na+ movement between different tissues and within the cell compartments are vital to understand the salt-tolerant mechanisms of plants. Here, we identified the GhBASS5 gene, a member of the bile acid sodium symporter (BASS) gene family from cotton, served as a plastidic Na+ transporter. GhBASS5 encodes a membrane protein localized in the plastid envelope. It was highly expressed in cotton roots and predominantly existed in the vascular cylinder. Heterogenous expression of GhBASS5 in Arabidopsis chloroplasts promoted Na+ uptake into chloroplasts, which contributed to an increased cytoplasmic Na+ concentration. And GhBASS5-overexpressed transgenic plants showed an increase in Na+ translocation from roots to shoots and an elevated Na+ content in both roots and shoots, but a dramatic decrease in the Na+ efflux from root tissues and the K+/Na+ ratio, especially under salt stress conditions. Furthermore, overexpressing GhBASS5 greatly damaged plastid functions and enhanced salt sensitivity in transgenic Arabidopsis when compared with wild-type plants under salt stress. Additionally, the salt-responsive transporter genes that regulate K+/Na+ homeostasis were dramatically expressed in GhBASS5-overexpressed lines, especially under salt stress conditions. Taken together, our results suggest that GhBASS5 is a plastid-localized Na+ transporter, and high expression of GhBASS5 impairs salt tolerance of plants via increasing Na+ transportation and accumulation at both cell and tissue levels.

Establishment of a transgene-free iPS cell line (SDQLCHi046-A) from a young patient bearing a HDAC8 mutation and suffering from Cornelia de Lange Syndrome.

In this study, peripheral blood mononuclear cells were isolated from a young male patient bearing a histone deacetyl-lase 8 (HDAC8) mutation and suffering from Cornelia de Lange Syndrome verified by clinical and genetic diagnosis. Induced pluripotent stem cells (iPSCs) were established by a non-integrative method, using plasmids carrying OCT4, SOX2, KLF4, BCL-XL and C-MYC. The established iPSCs presented typical pluripotent cells morphology, and expressed pluripotent stem cell markers at the mRNA and protein level. The iPSCs also showed differentiative capacity in vitro, and a normal karyotype. In addition, the established iPSCs still carried the HDAC8 mutation observed in the donor tissue.