Conclusion of diagnostic odysseys due to inversions disrupting and .

Many genetic testing methodologies are biased towards picking up structural variants (SVs) that alter copy number. Copy-neutral rearrangements such as inversions are therefore likely to suffer from underascertainment. In this study, manual review prompted by a virtual multidisciplinary team meeting and subsequent bioinformatic prioritisation of data from the 100K Genomes Project was performed across 43 genes linked to well-characterised skeletal disorders.

Correction: KAT6A Syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The clinical presentation caused by truncating CHD8 variants.

Variants in the chromodomain helicase DNA-binding protein 8 (CHD8) have been associated with intellectual disability (ID), autism spectrum disorders (ASDs) and overgrowth and CHD8 is one of the causative genes for OGID (overgrowth and ID). We investigated 25 individuals with CHD8 protein truncating variants (PTVs), including 10 previously unreported patients and found a male to female ratio of 2.7:1 (19:7) and a pattern of common features: macrocephaly (62.

KAT6A Syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants.

Purpose: Pathogenic variants in KAT6A have recently been identified as a cause of syndromic developmental delay. Within 2 years, the number of patients identified with pathogenic KAT6A variants has rapidly expanded and the full extent and variability of the clinical phenotype has not been reported.

Methods: We obtained data for patients with KAT6A pathogenic variants through three sources: treating clinicians, an online family survey distributed through social media, and a literature review.

2 new cases of pontocerebellar hypoplasia type 10 identified by whole exome sequencing in a Turkish family.

Pontocerebellar hypoplasia type 10 (PCH10) is a progressive autosomal recessive neurodegenerative disorder that has been recently described in association with cleavage and polyadenylation factor I subunit 1 (CLP1) mutations. To date, all reported cases have the same homozygous missense mutation in the CLP1 gene suggesting a founder mutation. CLP1 is an RNA kinase involved in tRNA splicing and maturation.