TNPO3

Limb-girdle muscular dystrophies (LGMDs) are clinically and genetically heterogeneous muscle disorders. We aimed to share the diagnostic yield of an NGS gene panel containing LGMD-related genes and our experience with LGMD.

Between February 2019 and October 2022, patients with a suspicion of LGMD and their relatives were reviewed in terms of demographic, clinical, and individual genetic data, age of symptom onset, sex, clinical features, LGMD types, cardiac involvement, muscle biopsy results, family history, and consanguinity. Our NGS gene panel consisted of ANO5, CAPN3, CAV3, DAG1, DES, DNAJB6, DYSF, FKTN, FLNC, FRKP, GAA, GMPPB, HNRNPDL, ISPD, LIMS2, LMNA, MYOT, PLEC, POMGNT1, POMK, POMT1, POMT2, SGCA, SGCB, SGCD, SGCG, TCAP, TNPO3, TRAPPC11, TRIM32, and TTN genes.

The diagnosis rate was 61.1% (11/18). Twelve (80%) patients with LGMD were male and three (20%) were female. The median age was 15.9 (range, 1.5-39) years. Our patient collective was drawn up out of patients with the following variants: LGMDR1 (n = 6; 40%), LGMDR2 (n = 4; 26.6%), LGMDR3 (n = 4; 26.6%), and LGMDR12 (n = 1; 6.7%).

The present study showed that the NGS panel has a high success rate in the diagnosis of LGMD and contributes to early diagnosis.

Rare and vulnerable endemic plants represent different evolutionary units that occur at different times, and protecting these species is a key issue in biological protection. Understanding the impact of the history of endangered plant populations on their genetic diversity helps to reveal evolutionary history and is crucial for guiding conservation efforts. Saussurea involucrata, a perennial alpine species mainly distributed in the Tianshan Mountains, is famous for its medicinal value but has become endangered due to over-exploitation. In the present study, we employed both nuclear and chloroplast DNA sequences to investigate the genetic distribution pattern and evolutionary history of S. involucrata. A total of 270 individuals covering nine S. involucrata populations were sampled for the amplification and sequencing of nrDNA Internal Transcribed Spacer (ITS) and chloroplast trnL-trnF, matK and ndhF-rpl32 sequences. Via calculation, we identified 7 nuclear and 12 plastid haplotypes. Among the nine populations, GL and BA were characterized by high haplotype diversity, whereas BG revealed the lowest haplotype diversity. Molecular dating estimations suggest that divergence among S. involucrata populations occurred around 0.75 Ma, coinciding with the uplift of Tianshan Mountains. Our results reveal that both isolation-by-distance (IBD) and isolation-by-resistance (IBR) have promoted genetic differentiation among populations of S. involucrata. The results from the ecological niche modeling analyses show a more suitable habitat for S. involucrata in the past than at present, indicating a historical distribution contraction of the species. This study provides new insight into understanding the genetic differentiation of S. involucrata, as well as the theoretical basis for conserving this species.

PTEN is a phosphoinositide lipid phosphatase and an important tumour suppressor protein. PTEN function is reduced or lost in around a third of all human cancers through diverse mechanisms, from gene deletion to changes in the function of proteins which regulate PTEN through direct protein binding. Here we present data from SILAC (Stable Isotope Labelling by Amino acids in Cell culture) proteomic screens to identify proteins which bind to PTEN. These experiments using untransformed epithelial cells and glioma cells identified several novel candidate proteins in addition to many previously identified PTEN binding partners and many proteins which are recognised as common false positives using these methods. From subsequent co-expression pull-down experiments we provide further evidence supporting the physical interaction of PTEN with MMP1, Myosin 18A and SHROOM3. We also performed yeast two-hybrid screens which identify the previously recognised PTEN binding partner MSP58 in addition to the nuclear import export receptor TNPO3. These experiments identify several novel candidate binding partners of PTEN and provide further data addressing the set of proteins that interact with this important tumour suppressor.