TCellSI: A Novel Method for T Cell State Assessment and Its Applications in Immune Environment Prediction

T cell is an indispensable component of the immune system and its multifaceted functions are shaped by the distinct T cell types and their various states. Although multiple computational models exist for predicting the abundance of diverse T cell types, tools for assessing their states to characterize their degree of resting, activation, and suppression are lacking. To address this gap, a robust and nuanced scoring tool called T cell state identifier (TCellSI) leveraging Mann-Whitne

Preimplantation genetic testing for Cockayne syndrome with a novel ERCC6 variant in a Chinese family

BackgroundCockayne syndrome (CS) is a rare, multisystem, autosomal recessive disorder characterized by cachectic dwarfism, nervous system abnormalities, and premature aging. Mutations in the ERCC6 and ERCC8 genes are the predominant causes of Cockayne syndrome, with ERCC6 gene mutations present in approximately 75% of cases.MethodsTrio-based whole-exome sequencing (trio-WES) was employed to identify potential pathogenic variants associated with CS. Preimplantation genetic testing for monogenic disorders (PGT-M) was conducted to prevent the transmission of the pathogenic variant.ResultsTwo compound heterozygous mutations were identified in ERCC6—c.1297G>T (p. Glu433*) and c.1607T>G (p. Leu536Trp)—with c.1297G>T representing a novel mutation. Four blastocysts resulting from intracytoplasmic sperm injection were subjected to biopsy. Genetic analyses revealed that E1 harbored maternal mutations in diploid embryos, E2 and E3 carried both paternal and maternal mutations in non-diploid embryos, and E4 did not carry paternal or maternal mutations in diploid embryos. Following the transfer of the E4 embryos, a single successful pregnancy was achieved.ConclusionThe successful application of PGT-M in this family offers a potential approach for addressing other monogenic diseases. The findings of this study broaden the variant spectrum of ERCC6 and will contribute to the molecular diagnosis and genetic counseling of CS. This case highlights the feasibility and effectiveness of PGT-M in preventing CS and provides valuable insights for similarly affected families

DNAH17 is associated with asthenozoospermia and multiple morphological abnormalities of sperm flagella.

BACKGROUND(#br)Multiple morphological abnormalities of the sperm flagella (MMAF) is one kind of severe asthenozoospermia, which is caused by dysplastic development of sperm flagella. In our study, we sought to investigate the novel gene mutations leading to severe asthenozoospermia and MMAF.(#br)METHODS AND MATERIALS(#br)The patient’s spermatozoa were tested by Papanicolaou staining and transmission electron microscopy. Whole exome sequencing was performed on the patient with severe asthenozoospermia and MMAF. Sanger sequencing verified the mutations in the family. The expression of DNAH17 was detected by immunofluorescence and Western blot.(#br)RESULTS(#br)Spermatozoa sample from the patient showed severe asthenozoospermia and MMAF. We detected biallelic mutations (c.C4445T, p.A1482V and c.C6857T, and p.S2286L) in DNAH17 (MIM:610063). The protein expression of DNAH17 was almost undetectable in spermatozoa from the patient with the biallelic mutations.(#br)CONCLUSION(#br)These results demonstrated that DNAH17 may be involved in severe asthenozoospermia and MMAF