BACKGROUND
Congenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis.
METHODS
We evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multi-center series of 42 persons with 16p11.2 deletions.
RESULTS
We identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P<3.8×10−6). These null alleles include copy-number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1 nonsense and 4 frame-shift mutations). However, the discordant intrafamilial phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null mutation is insufficient to cause congenital scoliosis. We went on to identify a common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null mutations (P<1.1×10−6). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the risk haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6-associated congenital scoliosis.
CONCLUSIONS
Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed.
TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model
Co S is considered a promising candidate as the anode material in lithium-ion batteries (LIBs) because of its remarkable electrical conductivity, high theoretical capacity, and low cost. However, the practical application of Co S is greatly restricted because of its poor cycling stability and rate performance, which result mainly from the large volume expansion and dissolution of the polysulfide intermediates during the charge/discharge process. In this report, Co S embedded in N-rich carbon hollow spheres are successfully designed and synthesized through an in situ pyrolysis and sulfurization process, employing the well-known ZIF-67 as the precursor and ethanethiol as the sulfur source. Co S nanoparticles embedded in the N-rich hollow carbon shell exhibit excellent lithium storage properties at a high charge/discharge rate. A discharge capacity of 784 mAh g is obtained upon battery testing at a current density of 1 C (544 mA g ). Even upon cycling at a current density of 4 C, the as-prepared Co S /N-C can still deliver a discharge capacity of 518 mAh g . The excellent battery performance can be attributed to the hollow structure as well as the N-rich carbon encapsulation. Moreover, this metal-organic framework sulfurization route also shows good generality for the synthesis of other metal sulfide-carbon composites such as ZnS/N-C and Cu S/C.
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