Publications by authors named "Tina Yee Ching Chan"

4 Publications

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Centrosome-associated CDC25B is a novel disease-causing gene for a syndrome with cataracts, dilated cardiomyopathy, and multiple endocrinopathies.

Clin Chim Acta 2020 May 3;504:81-87. Epub 2020 Feb 3.

Division of Chemical Pathology, Department of Pathology, Queen Mary Hospital, Hong Kong, China.

We describe a unique Chinese girl who presented with intrauterine growth retardation, delayed development, bilateral cataracts, hypothyroidism, growth hormone deficiency, and juvenile dilated cardiomyopathy. She was born to consanguineous parents with a history of one fetal and one infantile death in the family. She died from cardiac failure at the age of 12. In the pursuit of a diagnosis, the family was referred to the Clinics for Rare Diseases Referral and the University of Hong Kong Undiagnosed Disease Program. Whole-exome sequencing analysis revealed a homozygous non-sense variant, NM_021873:c.313G > T (p.Glu105*), in the CDC25B gene, a key regulator of the cell cycle. This variant was located in a region of homozygosity of 25 Mb on chromosome 20. Her parents and two asymptomatic sisters were confirmed to be carriers and one brother did not carry the variant. This is the first report of a natural human knockout of the CDC25B gene. Multiple endocrinopathies and fatal juvenile dilated cardiomyopathy suggests the potential for unfavorable complications in oncology patients receiving CDC25B inhibitors as an emerging targeted therapy.
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http://dx.doi.org/10.1016/j.cca.2020.01.017DOI Listing
May 2020

Clinical and pathological characterization of FLNC-related myofibrillar myopathy caused by founder variant c.8129G>A in Hong Kong Chinese.

Clin Genet 2020 05 23;97(5):747-757. Epub 2020 Feb 23.

Department of Pathology, Queen Elizabeth Hospital, Hong Kong.

FLNC-related myofibrillar myopathy could manifest as autosomal dominant late-onset slowly progressive proximal muscle weakness; involvements of cardiac and/or respiratory functions are common. We describe 34 patients in nine families of FLNC-related myofibrillar myopathy in Hong Kong ethnic Chinese diagnosed over the last 12 years, in whom the same pathogenic variant c.8129G>A (p.Trp2710*) was detected. Twenty-six patients were symptomatic when diagnosed; four patients died of pneumonia and/or respiratory failure. Abnormal amorphous material or granulofilamentous masses were detected in half of the cases, with mitochondrial abnormalities noted in two-thirds. We also show by haplotype analysis the founder effect associated with this Hong Kong variant, which might have occurred 42 to 71 generations ago or around Tang and Song dynasties, and underlain a higher incidence of myofibrillar myopathy among Hong Kong Chinese. The late-onset nature and slowly progressive course of the highly penetrant condition could have significant impact on the family members, and an early diagnosis could benefit the whole family. Considering another neighboring founder variant in FLNC in German patients, we advocate development of specific therapies such as chaperone-based or antisense oligonucleotide strategies for this particular type of myopathy.
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http://dx.doi.org/10.1111/cge.13715DOI Listing
May 2020

Case Report: The first probable Hong Kong Chinese case of -related acute recurrent rhabdomyolysis in a boy with two novel variants.

F1000Res 2019 2;8:1566. Epub 2019 Sep 2.

Kowloon West Cluster Laboratory Genetic Service, Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong, Laichikok, Hong Kong.

Recurrent rhabdomyolysis is frequently ascribed to fatty acid ß-oxidation defects, mitochondrial respiratory chain disorders and glycogen storage-related diseases. In recent years, autosomal recessive mutations have been identified as a prevailing cause of severe rhabdomyolysis in children in Western countries. We report the first probable Hong Kong Chinese case of recurrent severe rhabdomyolysis in early childhood caused by variants. Compound heterozygous novel variants NM_145693.2(LPIN1):c.[1949_1967dupGTGTCACCACGCAGTACCA]; [2410G>C] (p.[Gly657Cysfs*12];[Asp804His]) were detected. The former variant was classified as likely pathogenic while the latter variant was classified as a variant of uncertain significance (VUS) based on the guideline published by the American College of Medical Genetics and Genomics (ACMG) in 2015. Although the genetic findings were inconclusive, the patient's presentation was compatible with LPIN1-related acute recurrent rhabdomyolysis, and the patient was treated as such. The early recognition, timely diagnosis and management of this condition are important to avoid fatal consequences. To our knowledge, there has been no previous report in the English-language literature of a child with Chinese ethnicity and -related acute recurrent rhabdomyolysis (MIM #268200).  Functional characterization of the novel variants detected in this study are warranted in future studies.
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http://dx.doi.org/10.12688/f1000research.20343.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823901PMC
June 2020

Adulteration of proprietary Chinese medicines and health products with undeclared drugs: experience of a tertiary toxicology laboratory in Hong Kong.

Br J Clin Pharmacol 2018 Jan 4;84(1):172-178. Epub 2017 Oct 4.

Hospital Authority Toxicology Reference Laboratory, Princess Margaret Hospital, Hong Kong.

Aims: Proprietary Chinese medicines (pCMs) and health products, generally believed to be natural and safe, are gaining popularity worldwide. However, the safety of pCMs and health products has been severely compromised by the practice of adulteration. The current study aimed to examine the problem of adulteration of pCMs and health products in Hong Kong.

Methods: The present study was conducted in a tertiary referral clinical toxicology laboratory in Hong Kong. All cases involving the use of pCMs or health products, which were subsequently confirmed to contain undeclared adulterants, from 2005 to 2015 were reviewed retrospectively.

Results: A total of 404 cases involving the use of 487 adulterated pCMs or health products with a total of 1234 adulterants were identified. The adulterants consisted of approved drugs, banned drugs, drug analogues and animal thyroid tissue. The six most common categories of adulterants detected were nonsteroidal anti-inflammatory drugs (17.7%), anorectics (15.3%), corticosteroids (13.8%), diuretics and laxatives (11.4%), oral antidiabetic agents (10.0%) and erectile dysfunction drugs (6.0%). Sibutramine was the most common adulterant (n = 155). The reported sources of these illicit products included over-the-counter drug stores, the internet and Chinese medicine practitioners. A significant proportion of patients (65.1%) had adverse effects attributable to these illicit products, including 14 severe and two fatal cases. Psychosis, iatrogenic Cushing syndrome and hypoglycaemia were the three most frequently encountered adverse effects.

Conclusions: Adulteration of pCMs and health products with undeclared drugs poses severe health hazards. Public education and effective regulatory measures are essential to address the problem.
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http://dx.doi.org/10.1111/bcp.13420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736835PMC
January 2018
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