Front Cover: The cover image is based on the Research Article The transmission of human mitochondrial DNA in four-generation pedigrees by Sehrish Firyal et al., https://doi.org/10.1002/humu.24390.

We developed two tools to analyze and functionally classify miRNA variants.

Three novel variants in FHL1 associated with no FHL1 protein. Complete loss of all FHL1 isoforms leads to mild muscle affection and is more benign than the cytotoxic effects of expressed FHL1 protein associated with pathogenic missense variants.

Start codon-introducing 5'UTR NIPBL variants leading to repressed translation.

Three-step classification of Lynch syndrome-associated Variants of Uncertain Significance (VUSs) in any of the DNA mismatch repair genes. (1) Protein VUSs are synthesized in vitro, based on sequence information provided by the clinical geneticist. (2) Their functional activity are assayed and quantified. (3) The odds of pathogenicity are calculated and incorporated in the final classification according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology BS3/PS3 criteria

The frequency change of mitochondrial mutations across four generations.

De novo truncating NOVA2 variants lead to heterogeneous neurodevelopmental phenotypes. We identified novel clinical features (psychomotor regression, behavioral disturbances, dyspraxia, and urogenital and endocrinological manifestations), and showed that NOVA2 variants affect alternative splicing events.