Linlea Armstrong
A5014280043- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Neurofibromatosis and Schwannoma Cases
- Genomic variations and chromosomal abnormalities
- Autism Spectrum Disorder Research
- Cancer Genomics and Diagnostics
- BRCA gene mutations in cancer
- Prenatal Screening and Diagnostics
- Vascular Malformations Diagnosis and Treatment
- Congenital heart defects research
- Meningioma and schwannoma management
- Genetic Neurodegenerative Diseases
- Chromatin Remodeling and Cancer
- Genetic factors in colorectal cancer
- Bone Tumor Diagnosis and Treatments
- Ion channel regulation and function
- Neuroblastoma Research and Treatments
- Neurogenetic and Muscular Disorders Research
- Biomedical Ethics and Regulation
- Soft tissue tumor case studies
- Tracheal and airway disorders
- Connective tissue disorders research
- Urological Disorders and Treatments
- Congenital limb and hand anomalies
- RNA Research and Splicing
University of British Columbia
2015-2024
British Columbia Children's Hospital
2016-2024
IHS Markit (United States)
2024
Vancouver Biotech (Canada)
2024
B.C. Women's Hospital & Health Centre
2013-2023
Children's & Women's Health Centre of British Columbia
2006-2023
BC Cancer Agency
2009-2022
Vancouver General Hospital
2022
University of Siena
2021
Azienda Ospedaliera Universitaria Senese
2021
Whole-exome sequencing has transformed gene discovery and diagnosis in rare diseases. Translation into disease-modifying treatments is challenging, particularly for intellectual developmental disorder. However, the exception inborn errors of metabolism, since many these disorders are responsive to therapy that targets pathophysiological features at molecular or cellular level.To uncover genetic basis potentially treatable we combined deep clinical phenotyping (the comprehensive...
We report 281 individuals carrying a pathogenic recurrent NF1 missense variant at p.Met1149, p.Arg1276, or p.Lys1423, representing three nontruncating hotspots in the University of Alabama Birmingham (UAB) cohort, together identified 1.8% unrelated individuals. About 25% (95% confidence interval: 20.5–31.2%) heterozygous for p.Lys1423 had Noonan-like phenotype, which is significantly more compared with "classic" NF1-affected cohorts (all p < .0001). Furthermore, p.Arg1276 and variants were...
Abstract Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous these...
Abstract The role for routine whole genome and transcriptome analysis (WGTA) poor prognosis pediatric cancers remains undetermined. Here, we characterize somatic mutations, structural rearrangements, copy number variants, gene expression, immuno-profiles germline cancer predisposition variants in children adolescents with relapsed, refractory or malignancies who underwent WGTA matched sequencing. Seventy-nine participants a median age at enrollment of 8.8 y (range 6 months to 21.2 y) are...
Abstract Kabuki syndrome is a multiple congenital anomaly/mental retardation syndrome. This study of had two objectives. The first was to further describe the features. In order do so, clinical geneticists were asked submit cases—providing photographs and completing phenotype questionnaire for individuals in whom they felt diagnosis secure. All submitted cases reviewed by four diagnosticians familiar with agreed upon 48 previously unpublished individuals. Our data on these show that variably...
Prompt recognition of a child with cancer predisposition syndrome (CPS) has implications for management, surveillance, genetic counseling, and cascade testing relatives. Diagnosis CPS requires practitioner expertise, access to testing, test result interpretation. This diagnostic process is not accessible in all institutions worldwide, leading missed diagnoses. Advances electronic health technology can facilitate risk assessment.To evaluate the accuracy prediction tool (McGill Interactive...
Abstract Background Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, British Columbia, Canada, offered screening both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than but costly produces false positive results. The purpose this study was calculate the cost-effectiveness for BRCA1/2 mutation carriers a Canadian setting. Methods We constructed Markov model annual carriers, using local data...
Abstract Background Congenital fibrosis of the extraocular muscles types 1 and 3 (CFEOM1/CFEOM3) are autosomal dominant strabismus disorders that appear to result from maldevelopment ocular nuclei nerves. We previously reported most individuals with CFEOM1 rare CFEOM3 harbor heterozygous mutations in KIF21A . encodes a kinesin motor involved anterograde axonal transport, familial de novo date predictably alter one only few amino acids – three within third coiled-coil region stalk distal...
Abstract Episodic Ataxia Type 1 is an autosomal dominant disorder characterized by episodes of ataxia and myokymia. It associated with mutations in the KCNA1 voltage‐gated potassium channel gene. In present study, we describe a family novel clinical features including persistent cerebellar dysfunction, atrophy, cognitive delay. All affected members have myokymia epilepsy, but only one individual has vertigo. Additional include postural abnormalities, episodic stiffness weakness. A mutation...
Lynch syndrome is defined by the presence of germline mutations in mismatch repair (MMR) genes. Several models have been recently devised that predict mutation carrier status (Myriad Genetics, Wijnen, Barnetson, PREMM and MMRpro models). Families at moderate-high risk for harboring a Lynch-associated mutation, referred to BC Cancer Agency (BCCA) Hereditary Program (HCP), underwent analysis, immunohistochemistry and/or microsatellite testing. Seventy-two tested cases were included....
Genome-wide sequencing (GWS) is a standard of care for diagnosis suspected genetic disorders, but the proportion patients found to have pathogenic or likely variants ranges from less than 30% more 60% in reported studies. It has been suggested that diagnostic rate can be improved by interpreting genomic context each affected individual's full clinical picture and regular follow-up reinterpretation GWS laboratory results. Trio exome was performed 415 families trio genome 85 CAUSES study. The...
Abstract The characteristic sites of Neurofibromatosis 1‐associated osseous manifestations are the long bones (usually tibia and fibula), vertebrae sphenoid wing. Although these focal bony lesions may cause profound clinical consequences, a minority people with NF1 affected. However, most shorter than expected for their age, gender family. pathogenesis osteopathy its relationship, if any, to short stature unknown. We examined associations between occurrence various in 3377 probands from...
Abstract The neonate born small for gestational age (SGA, birth weight <10th centile) with severe hypospadias, and without the presence of other malformations, is a presentation which clinical geneticists are asked to assess. However, this combination not well addressed in literature. Epidemiological studies point an increased incidence severity hypospadias SGA infants, but leave open possibility that association attributable population subset who have multiple congenital abnormalities or...
Identifying genetic mosaicism is important in establishing a diagnosis, assessing recurrence risk, and providing accurate counseling. Next-generation sequencing has allowed for the identification of at levels below those detectable by conventional Sanger or chromosomal microarray analysis. The CAUSES Clinic was pediatric translational trio-based genome-wide (exome genome) study 500 families (531 children) with suspected disease BC Children's Women's Hospitals. Here we present 12 cases...
Abstract People with neurofibromatosis 1 (NF1) have low bone mineralization, but the natural history and pathogenesis are poorly understood. We performed a sibling‐matched case–control study of mineral status, morphology, metabolism. Eighteen children NF1 without focal bony lesions were compared to unaffected siblings local population controls. Bone content at lumbar spine proximal femur (dual energy X‐ray absorptiometry (DXA)) was lower in NF1; this difference persisted after adjusting for...