CDK13-Related Disorder: Novel Insights From A Series of 27 Cases and Recommendations for Clinical Management.

In 2016, Sifrim and colleagues described the first group of patients carrying heterozygous pathogenic variants in CDK13 and sharing major clinical features mainly consisting of congenital heart defects, intellectual disability and peculiar facial features (Congenital Heart Defects, Dysmorphic Facial Features, and Intellectual Developmental Disorder; CHDFIDD, OMIM # 617360). This condition is generally referred to as CDK13-related disorder, and since then other reports have provided further clinical and molecular information. Here we describe a group of 27 previously unreported patients to more accurately profile the clinical spectrum associated with CDK13 variants, disclosing novel associated findings, such as complex craniosynostosis and variable skeletal features (e.

Effectiveness and Impact of Transcript Analysis in Clinical Genetics Daily Practice.

Broad-spectrum genetic tests often lead to the identification of variants of uncertain significance (VUS), a major issue in modern clinical genetics. A fair proportion of VUS may alter the splicing processes, but their interpretation is challenging. This study aimed at providing a classification approach for VUS potentially-affecting splicing by integrating transcript analysis from peripheral blood mRNA into routine diagnostics.

Two more families supporting the existence of monogenic spinocerebellar ataxia 48.

The reduced penetrance of TBP intermediate alleles and the recently proposed possible digenic TBP/STUB1 inheritance raised questions on the possible mechanism involved opening a debate on the existence of SCA48 as a monogenic disorder. We here report clinical and genetic results of two apparently unrelated patients carrying the same STUB1 variant(c.244G > T;p.