Front Cover: The cover image is based on the Research Article Novel CIC variants identified in individuals with neurodevelopmental phenotypes by Qiumin Tan et al., https://doi.org/10.1002/humu.24346.

Back Cover: The cover image is based on the Research Article Phenotypic and mutational spectrum of ROR2-related Robinow syndrome by Juliana Forte Mazzeu de Araujo et al., https://doi.org/10.1002/humu.24375.

The paradigm of opposing phenotypes for both FBN1 and FBN2 suggests shared pathomechanisms.

Comprehensive overview of the CNGA3 variant spectrum extending it to 316 variants.

Software for easy detection of disease causing short tandem repeat expansions

Although rare, detecting three or more disease-causing variants in a patient's gene can be puzzling. Nanopore Cas9-targeted sequencing deciphers the pathogenic variants by precise haplotyping in such cases.

If the risk associated with pathogenic variants (PV) in a gene is known genetic case-control studies can be used to estimate how many typical PV are present in a set observed variants. We describe a simple maximum likelihood calculation for this purpose and use it to show that for breast cancer predisposition genes a small but important group of pathogenic variants are located in non-coding regions and that the proportion and location of pathogenic missense variants varies greatly between genes.

Heterozygous CIC pathogenic variants have been identified in individuals with neurodevelopmental phenotypes. Here, we describe three novel and one previously reported CIC variants in four individuals with neurodevelopmental delay.

Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive Robinow syndrome trait phenotype with multiple skeletal defects. Molecular diagnosis and a comprehensive quantitative clinical evaluation delineated the phenotypic spectrum of ROR2-related Robinow syndrome.

Loss-of-function (LoF) LZTR1 variants have been associated with schwannomatosis. However, many LoF LZTR1 variants exist in Genome Aggregation Database (gnomAD) in people who do not have clinical symptoms of schwannomatosis. We show here that LoF LZTR1 variants are strongly enriched in schwannomatosis patients, but the high frequency of LoF LZTR1 variants in gnomAD data suggest a reduced risk of schwannomas in comparison to other schwannoma predisposing genes.

Effects of 14 F9 synonymous codon variants on hemophilia B expression: alteration of splicing along with protein expression. The impacts of 14 F9 SCVs on splicing and protein expression were detected using a combination of in silico prediction, in vitro minigene assay and cell expression detection. 5 SCVs produced almost all aberrant splicing isoforms, and 3 SCVs presented a partial defect in both splicing and protein secretion. The rest 6 SCVs had no effect on neither splicing nor protein expression.

Genetics plays a substantial role in the etiology of neurodevelopmental disorders. By trio whole-exome sequencing, three unrelated patients with a spectrum of neurological and developmental phenotypes carrying compound heterozygous variants in DNAH14 were identified, which indicated that variants in DNAH14 could lead to previously unrecognized neurodevelopmental disorders.