Dissecting CASK: Novel splice site variant associated with male MICPCH phenotype.

CASK (MIM#300172), encoding a calcium/calmodulin-dependent serine protein kinase, is crucial for synaptic transmission and gene regulation during neural development. Pathogenic variants of CASK are known to cause several neurodevelopmental disorders, including X-linked intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH). This study introduces a novel, de novo synonymous CASK variant (NM_001367721.

: An R package for the analysis of very low frequency variants in DNA sequences.

Here, we introduce , an R package to determine the distribution of very low frequency variants (VLFs) in nucleotide and amino acid sequences for the analysis of errors in DNA sequence records. The package allows users to assess VLFs in aligned and trimmed protein-coding sequences by automatically calculating the frequency of nucleotides or amino acids in each sequence position and outputting those that occur under a user-specified frequency (default of = 0.001).

Spondyloepimetaphyseal dysplasia with joint laxity type 2: Aggregating the literature and reporting on the life of a 66-year-old man.

Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (SEMDJL2), is a rare bone dysplasia that results from hotspot (amino acids148/149) mutations in KIF22. Clinically, affected individuals present with generalized joint laxity, limb malalignment, midface hypoplasia, gracile digits, postnatal short stature, and occasionally, tracheolaryngomalacia; additionally, radiological features include severe epi-metaphyseal abnormalities and slender metacarpals. This report evaluates the progression of SEMDJL2 throughout the life of the oldest individual reported in the literature-a 66-year-old man with a pathogenic KIF22 variant (c.

Diagnostic yield of clinical exome sequencing in adulthood in medical genetics clinics.

Clinical exome sequencing (ES) is the most comprehensive genomic test to identify underlying genetic diseases in Canada. We performed this retrospective cohort study to investigate the diagnostic yield of clinical ES in adulthood. Inclusion criteria were: (1) Adult patients ≥18 years old; (2) Patients underwent clinical ES between January 1 and December 31, 2021; (3) Patients were seen in the Department of Medical Genetics.

Outcomes of mitochondrial long chain fatty acid oxidation and carnitine defects from a single center metabolic genetics clinic.

Background: Mitochondrial long-chain fatty acid oxidation and carnitine metabolism defects are a group of inherited metabolic diseases. We performed a retrospective cohort study to report on the phenotypic and genotypic spectrum of mitochondrial long-chain fatty acid oxidation and carnitine metabolism defects as well as their treatment outcomes.

Methods: All patients with mitochondrial long-chain fatty acid oxidation and carnitine metabolism defects were included.

Prevalence of Congenital Disorders of Glycosylation in Childhood Epilepsy and Effects of Anti-Epileptic Drugs on the Transferrin Isoelectric Focusing Test.

Introduction: Childhood epilepsy is one of the most common neurological problems. The transferrin isoelectric focusing (TIEF) test is a screening test for congenital disorders of glycosylation (CDG). We identified abnormal TIEF test in children with epilepsy in our epilepsy genetics clinic.

Canada-Wide Epidemic of Group A Invasive Disease.

Background: The number of invasive group A (iGAS) infections due to hitherto extremely rare type strains has increased in several Canadian provinces since late 2015. We hypothesized that the cases recorded in the different provinces are linked and caused by strains of an clone that recently emerged and expanded explosively.

Methods: We analyzed both active and passive surveillance data for iGAS infections and used whole-genome sequencing to investigate the phylogenetic relationships of the strains responsible for these invasive infections country-wide.

Use of Genome Sequencing to Define Institutional Influenza Outbreaks, Toronto, Ontario, Canada, 2014-15.

Adequacy of the current clinical definition of institutional influenza outbreaks is unclear. We performed a retrospective genome sequencing and epidemiologic analysis of institutional influenza outbreaks that occurred during the 2014-15 influenza season in Toronto, Canada. We sequenced the 2 earliest submitted samples positive for influenza A(H3N2) from each of 38 reported institutional outbreaks in long-term care facilities.

A single amino acid polymorphism in the glycosyltransferase CpsK defines four Streptococcus suis serotypes.

The capsular polysaccharide (CPS) is the major virulence factor of the emerging zoonotic pathogen Streptococcus suis. CPS differences are also the basis for serological differentiation of the species into 29 serotypes. Serotypes 2 and 1/2, which possess identical gene content in their cps loci, express CPSs that differ only by substitution of galactose (Gal) by N-acetylgalactosamine (GalNAc) in the CPS side chain.

Distribution of Suicin Gene Clusters in Serotype 2 Belonging to Sequence Types 25 and 28.

Recently, we reported the purification and characterization of three distinct lantibiotics (named suicin 90-1330, suicin 3908, and suicin 65) produced by . In this study, we investigated the distribution of the three suicin lantibiotic gene clusters among serotype 2 strains belonging to sequence type (ST) 25 and ST28, the two dominant STs identified in North America. The genomes of 102 strains were interrogated for the presence of suicin gene clusters encoding suicins 90-1330, 3908, and 65.

Capsular Switching and Other Large-Scale Recombination Events in Invasive Sequence Type 1 Group B Streptococcus.

We report several cases of recombination events leading to capsular switching among sequence type (ST) 1 group B Streptococcus strains. These strains otherwise shared a common genome backbone with serotype V ST1 strains. However, the genomes of ST1 serotype V strains and those of serotypes VI, VII, and VIII strains differed substantially.

Comparative Genome Analyses of Streptococcus suis Isolates from Endocarditis Demonstrate Persistence of Dual Phenotypic Clones.

Many bacterial species coexist in the same niche as heterogeneous clones with different phenotypes; however, understanding of infectious diseases by polyphenotypic bacteria is still limited. In the present study, encapsulation in isolates of the porcine pathogen Streptococcus suis from persistent endocarditis lesions was examined. Coexistence of both encapsulated and unencapsulated S.

High Incidence of Invasive Group A Streptococcus Disease Caused by Strains of Uncommon emm Types in Thunder Bay, Ontario, Canada.

An outbreak of type emm59 invasive group A Streptococcus (iGAS) disease was declared in 2008 in Thunder Bay District, Northwestern Ontario, 2 years after a countrywide emm59 epidemic was recognized in Canada. Despite a declining number of emm59 infections since 2010, numerous cases of iGAS disease continue to be reported in the area. We collected clinical information on all iGAS cases recorded in Thunder Bay District from 2008 to 2013.

Complex Population Structure and Virulence Differences among Serotype 2 Streptococcus suis Strains Belonging to Sequence Type 28.

Streptococcus suis is a major swine pathogen and a zoonotic agent. Serotype 2 strains are the most frequently associated with disease. However, not all serotype 2 lineages are considered virulent.

Emergence of Serotype IV Group B Streptococcus Adult Invasive Disease in Manitoba and Saskatchewan, Canada, Is Driven by Clonal Sequence Type 459 Strains.

Serotype IV group B Streptococcus (GBS) is emerging in Canada and the United States with rates as high as 5% of the total burden of adult invasive GBS disease. To understand this emergence, we studied the population structure and assessed the antimicrobial susceptibility of serotype IV isolates causing adult invasive infection in Manitoba and Saskatchewan, Canada, between 2010 and 2014. Whole-genome sequencing was used to determine multilocus sequence typing information and identify genes encoding antimicrobial resistance in 85 invasive serotype IV GBS strains.

Deriving group A Streptococcus typing information from short-read whole-genome sequencing data.

Typing of group A Streptococcus (GAS) is crucial for infection control and epidemiology. While whole-genome sequencing (WGS) is revolutionizing the way that bacterial organisms are typed, it is necessary to provide backward compatibility with currently used typing schemas to facilitate comparisons and understanding of epidemiological trends. Here, we sequenced the genomes of 191 GAS isolates representing 42 different emm types and used bioinformatics tools to derive commonly used GAS typing information directly from the short-read WGS data.