From bench to in silico and backwards: What have we done on genetics of recurrent pregnancy loss and implantation failure and where should we go next?

Human reproduction goes through many challenges to its success and in many cases it fails. Cases of pregnancy loss are common outcomes for pregnancies, and implantation failures (IF) are common in assisted reproduction attempts. Although several risk factors have already been linked to adverse outcomes in reproduction, many cases remain without a definitive cause.

CNOT1 p.Arg535Cys variant in holoprosencephaly with late onset diabetes mellitus.

Holoprosencephaly (HPE) results from a lack of cleavage of the prosencephalon. It has a complex etiology, resulting from chromosome abnormalities or single gene variants in the Sonic hedgehog signaling pathway. A single variant, p.

Congenital anomalies in pregnancies with overt and pregestational type 2 diabetes: a gray portrayal from a cohort in Brazil.

Objective: To describe the frequency and types of congenital anomalies and associated risk factors in Brazilian women with type 2 diabetes.

Methods: In this retrospective cohort study between 2005 and 2021, we included all pregnant participants with type 2 diabetes from the two major public hospitals in southern Brazil. We collected data from the electronic hospital records.

Identification of a founder effect involving n.197C>T variant in RMRP gene associated to cartilage-hair hypoplasia syndrome in Brazilian patients.

Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder frequently linked to n.72A>G (previously known as n.70A>G and n.

A germline chimeric KANK1-DMRT1 transcript derived from a complex structural variant is associated with a congenital heart defect segregating across five generations.

Structural variants (SVs) pose a challenge to detect and interpret, but their study provides novel biological insights and molecular diagnosis underlying rare diseases. The aim of this study was to resolve a 9p24 rearrangement segregating in a family through five generations with a congenital heart defect (congenital pulmonary and aortic valvular stenosis and pulmonary artery stenosis), by applying a combined genomic analysis. The analysis involved multiple techniques, including karyotype, chromosomal microarray analysis (CMA), FISH, genome sequencing (GS), RNA-seq, and optical genome mapping (OGM).