BackgroundWiedemann–Steiner syndrome (WDSTS) is a rare genetic disorder characterized by facial gestalt, neurodevelopmental delay, skeletal anomalies and growth retardation, which is caused by variation of KMT2A gene. To date, only 2 Chinese WDSTS patients have been reported. Here, we report the phenotypes and KMT2A gene variations in 14 unrelated Chinese WDSTS patients and investigate the phenotypic differences between the Chinese and French cohorts. MethodsNext generation sequencing was performed for each patient, and the variants in the KMT2A gene were validated by Sanger sequencing. The phenotypes of 16 Chinese WDSTS patients were summarized and compared to 33 French patients.ResultsGenetic sequencing identified 13 deleterious de novo KMT2A variants in 14 patients, including 10 truncating, 2 missenses and 1 splicing variants. Of the 13 variants, 11 are novel and two have been reported previously. One of the patients is mosaic in the KMT2A gene. The variation spectra and phenotypic profiles of the Chinese WDSTS patients showed no difference with patients of other ethnicities; however, differ in the frequencies of several clinical features. We demonstrated that variations in the KMT2A gene can lead to both advanced and delayed bone age. We identified 6 novel phenotypes, which include microcephaly, deep palmar crease, external ear deformity, carpal epiphyseal growth retardation, dyslipidemia, and glossoptosis. In addition, patients harbored missense variants in the CXXC zinc finger domain of KMT2A showed more severe neurophenotypes.ConclusionOur study consists of the largest cohort of Chinese WDSTS patients that continues to expand the WDSTS phenotypic and variation spectrum. Our results support the notion that the CXXC zinc finger domain of KMT2A gene is a hotspot for missense variants associated with more severe neurophenotypes.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0909-0) contains supplementary material, which is available to authorized users.

Tissue optical clearing enables imaging deeper in large volumes with high-resolution. ClearT2 is a relatively rapid clearing method with no use of solvents or detergents, hence poses great advantage on preservation of diverse fluorescent labels. However, this method suffers from insufficient tissue transparency, especially for adult mouse brain blocks. In this work, we develop a rapid and versatile clearing method based on ClearT2, termed RTF (Rapid clearing method based on Triethanolamine and Formamide), aiming for better clearing capability. The results show that RTF can not only efficiently clear embryos, neonatal brains and adult brain blocks, but also preserve fluorescent signal of both endogenous fluorescent proteins and lipophilic dyes, and be compatible with virus labeling and immunostaining. With the good transparency and versatile compatibility, RTF allows visualization and tracing of fluorescent labeling cells and neuronal axons combined with different imaging techniques, showing potentials in facilitating observation of morphological architecture and visualization of neuronal networks.

Seed dormancy and germination are important agronomic traits in wheat (Triticum aestivum L.) because they determine pre-harvest sprouting (PHS) resistance and thus affect grain production. These processes are regulated by Gibberellic Acid-Stimulated Regulator (GASR) genes. In this study, we identified 37 GASR genes in common wheat, which were designated TaGASR1-37. Moreover, we identified 40 pairs of paralogous genes, of which only one had a Ka/Ks value greater than 1, indicating that most TaGASR genes have undergone negative selection. Chromosomal location and duplication analysis revealed 25 pairs of segmentally duplicated genes and seven pairs of tandemly duplicated genes, suggesting that large-scale duplication events may have contributed to the expansion of TaGASR gene family. Microarray analysis of the expression of 18 TaGASR genes indicated that these genes play diverse roles in different biological processes. Using wheat varieties with contrasting seed dormancy phenotypes, we investigated the expression patterns of TaGASR genes and the corresponding seed germination index phenotypes in response to water imbibition, exogenous ABA and GA treatment, and low- and high-temperature treatment. Based on these data, we identified the TaGASR34 gene as potentially associated with seed dormancy and germination. Further, we used a SNP mutation of the TaGASR34 promoter (-16) to develop the CAPS marker GS34-7B, which was then used to validate the association of TaGASR34 with seed dormancy and germination by evaluating two natural populations across environments. Notably, the frequency of the high-dormancy GS34-7Bb allele was significantly lower than that of the low-dormancy GS34-7Ba allele, implying that the favorable GS34-7Bb allele has not previously been used in wheat breeding. These results provide valuable information for further functional analysis of TaGASR genes and present a useful gene and marker combination for future improvement of PHS resistance in wheat.

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