7 results match your criteria: "University of British Columbia and Women's Hospital of British Columbia[Affiliation]"
Generation of tandem alternative splice acceptor sites and CLTC haploinsufficiency: A cause of CLTC-related disorder.
Am J Med Genet A
August 2023
The Rare Disease Discovery Hub, BC Children's Hospital Research Institute, University of British Columbia and Children's Hospital of British Columbia, Vancouver, British Columbia, Canada.
Tandem splice acceptors (NAGN AG) are a common mechanism of alternative splicing, but variants that are likely to generate or to disrupt tandem splice sites have rarely been reported as disease causing. We identify a pathogenic intron 23 CLTC variant (NM_004859.4:c.
View Article and Find Full Text PDFDo PACS1 variants impeding adaptor protein binding predispose to syndromic intellectual disability?
Am J Med Genet A
August 2023
Department of Medical Genetics and Provincial Medical Genetics Program, University of British Columbia and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
Article Synopsis
- PACS1-neurodevelopmental disorder (PACS1-NDD) is linked to a specific genetic variation, Arg203, which causes a type of intellectual disability due to its effect on PACS1 protein's client protein interactions.
- Researchers hypothesize that other PACS1 variants that disrupt binding to adaptor proteins could also lead to similar intellectual disabilities.
- A novel PACS1 variant (Ser252Phe) was identified in a mother-daughter pair, which may impair binding to an adaptor protein (GGA3), suggesting it could contribute to PACS1-NDD-like symptoms and enhancing understanding of how PACS1 variations cause intellectual disabilities.
Can tandem alternative splicing and evasion of premature termination codon surveillance contribute to attenuated Peutz-Jeghers syndrome?
Am J Med Genet A
October 2022
Imagenetics, Sanford Health and Research Center and Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota, USA.
Alternative use of short distance tandem sites such as NAGN AG are a common mechanism of alternative splicing; however, single nucleotide variants are rarely reported as likely to generate or to disrupt tandem splice sites. We identify a pathogenic intron 5 STK11 variant (NM_000455.4:c.
View Article and Find Full Text PDFCan leaky splicing and evasion of premature termination codon surveillance contribute to the phenotypic variability in Alkuraya-Kucinskas syndrome?
Eur J Med Genet
March 2022
Department of Medical Genetics and Provincial Medical Genetics Program, University of British Columbia and Women's Hospital of British Columbia, Vancouver, BC, Canada.
Article Synopsis
- KIAA1109 variants are linked to Alkuraya-Kucinskas syndrome, which causes issues like cerebral underdevelopment, clubfeet, and arthrogryposis, with severity depending on the type of genetic change.
- Severe cases often stem from biallelic truncating variants leading to miscarriage or early death, while milder forms may result from biallelic missense variants causing developmental delays.
- A family study revealed a specific splice donor mutation in KIAA1109, resulting in partial mRNA skipping, which may explain the milder phenotypes seen in some patients.
An infant with congenital respiratory insufficiency and diaphragmatic paralysis: A novel BICD2 phenotype?
Am J Med Genet A
March 2022
Department of Medical Genetics and Provincial Medical Genetics Program, University of British Columbia and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
Monoallelic pathogenic variants in BICD2 are associated with autosomal dominant Spinal Muscular Atrophy Lower Extremity Predominant 2A and 2B (SMALED2A, SMALED2B). As part of the cellular vesicular transport, complex BICD2 facilitates the flow of constitutive secretory cargoes from the trans-Golgi network, and its dysfunction results in motor neuron loss. The reported phenotypes among patients with SMALED2A and SMALED2B range from a congenital onset disorder of respiratory insufficiency, arthrogryposis, and proximal or distal limb weakness to an adult-onset disorder of limb weakness and contractures.
View Article and Find Full Text PDFMesenteric cysts, lymphatic leak, and cerebral cavernous malformation in a proband with KRIT1-related disease.
Am J Med Genet A
January 2022
Department of Medical Genetics and Provincial Medical Genetics Program, University of British Columbia and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
Cerebral cavernous malformations (CCMs) of the central nervous system arise sporadically or secondary to genomic variation. Established genetic etiologies include deleterious variants in KRIT1 (CCM1), malcavernin (CCM2), and PDCD10 (CCM3). KRIT1-related disease has not been described in conjunction with lymphatic defects, although lymphatic defects with abnormal endothelial cell junctions have been observed in mice deficient in HEG1-KRIT1 signaling.
View Article and Find Full Text PDFAn approach to rapid characterization of DMD copy number variants for prenatal risk assessment.
Am J Med Genet A
August 2021
Department of Medical Genetics and Provincial Medical Genetics Program, University of British Columbia and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
Prenatal detection of structural variants of uncertain significance, including copy number variants (CNV), challenges genetic counseling, and creates ambiguity for expectant parents. In Duchenne muscular dystrophy, variant classification and phenotypic severity of CNVs are currently assessed by familial segregation, prediction of the effect on the reading frame, and precedent data. Delineation of pathogenicity by familial segregation is limited by time and suitable family members, whereas analytical tools can rapidly delineate potential consequences of variants.
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