Biomedical subjects

Victoria Mok Siu

Publications and source records attributed to Victoria Mok Siu.

4 recordsLinked to original sources

PubMed2026

Histidine Supplementation Stabilizes Hearing and Vision and Improves Growth in HARS1-Related Autosomal Recessive Disorder Associated With Usher-Like Symptoms.

Autosomal recessive HARS1-related disorder (originally described as Usher syndrome type 3B) caused by a homozygous Y454S variant in the histidyl-tRNA synthetase gene (HARS1) is characterized by progressive sensorineural hearing and vision loss and respiratory deterioration with risk for sudden death following febrile illnesses. In-vitro studies have previously shown that histidine can rescue a humanized yeast model for pathogenic HARS alleles. Fourteen children homozygous for HARS Y454S were treated with supplemental oral histidine (50 mg/kg BID) and monitored with bloodwork and physical, visual, and audiometry assessments during a 3-year clinical trial, then followed for more than 4 years on histidine in the post-trial period. Patient fibroblasts were assessed for response to histidine. Hearing and vision remained stable, and growth improved significantly. Children remained healthy, with no severe deteriorations despite exposure to bacterial and viral infections, including COVID-19. Gains in growth were maintained in the post-trial period on varying levels of histidine supplementation. Daily oral histidine supplementation in children with autosomal recessive HARS1-related disorder can ameliorate or slow the progression of disease and is safe, inexpensive, and well tolerated. This study adds to the growing list of autosomal recessive ARSopathies (aminoacyl-tRNA synthetase disorders) that are amenable to amino acid supplementation.

Humans↗

PubMed2025

Mainstreaming of clinical genetic testing: A conceptual framework.

PURPOSE: Demand for genetic testing is increasing across medicine, whereas the genetics workforce remains stable. In response, mainstreaming models are being introduced, in which nongeneticist clinicians are increasingly involved in the genetic testing pathway. Because a standardized approach would facilitate evaluation and optimal patient care, a unified framework is warranted. METHODS: Through a focus group with clinical genetics experts, a conceptual framework for the mainstreaming of clinical genetic testing is proposed. Through a consensus process, experts elucidated the steps in the diagnostic care pathway and defined a set of variables that influence which mainstreaming model is best suited to specific patient care scenarios. RESULTS: A total of 35 individuals representing 20 distinct clinical genetics services and all Canadian provinces participated in the development of the framework. The framework describes 4 generalizable mainstreaming models of care, each with varying levels of involvement of the clinical genetics service in the diagnostic care pathway. CONCLUSION: This framework will help guide clinical teams in the design and evaluation of mainstreaming efforts. It is critical that these programs are evaluated and shared in a standardized way so that we can implement strategies that allow optimal utilization of genetics resources and improve patient care.

Humans↗

PubMed2006

Breakpoint Associated with a novel 2.3 Mb deletion in the VCFS region of 22q11 and the role of Alu (SINE) in recurring microdeletions.

BACKGROUND: Chromosome 22q11.2 region is highly susceptible to rearrangement, specifically deletions that give rise to a variety of genomic disorders including velocardiofacial or DiGeorge syndrome. Individuals with this 22q11 microdeletion syndrome are at a greatly increased risk to develop schizophrenia. METHODS: Genotype analysis was carried out on the DNA from a patient with the 22q11 microdeletion using genetic markers and custom primer sets to define the deletion. Bioinformatic analysis was performed for molecular characterization of the deletion breakpoint sequences in this patient. RESULTS: This 22q11 deletion patient was established to have a novel 2.3 Mb deletion with a proximal breakpoint located between genetic markers RH48663 and RH48348 and a distal breakpoint between markers D22S1138 and SHGC-145314. Molecular characterization of the sequences at the breakpoints revealed a 270 bp shared sequence of the breakpoint regions (SSBR) common to both ends that share >90% sequence similarity to each other and also to short interspersed nuclear elements/Alu elements. CONCLUSION: This Alu sequence like SSBR is commonly in the proximity of all known deletion breakpoints of 22q11 region and also in the low copy repeat regions (LCRs). This sequence may represent a preferred sequence in the breakpoint regions or LCRs for intra-chromosomal homologous recombination mechanisms resulting in common 22q11 deletion.

Adolescent↗

PubMed2005

Bilateral complete isolated cryptophthalmos: a case report.

Cryptophthalmos is a condition of congenital eyelid malformation most commonly accompanied by syndactyly, urogenital anomalies, and cognitive impairments as in Fraser syndrome. We report on a patient with characteristic features consistent with autosomal dominant bilateral complete isolated cryptophthalmos. This patient represents only the sixth documented case of bilateral complete isolated cryptophthalmos. Defining characteristics of this variety are discussed, including bilateral central dimpling over the globes, normal eyebrow growth, and the absence of cognitive impairment. We introduce phenotypic features that distinguish bilateral isolated cryptophthalmos from other forms and discuss its relatively favorable prognosis.

Abnormalities, Multiple↗