Publications by authors named "Luen-Cheung Ho"

7 Publications

  • Page 1 of 1

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

Founder Mutation c.1516A>C in KLHL40 Is a Frequent Cause of Nemaline Myopathy With Hyponatremia in Ethnic Chinese.

J Neuropathol Exp Neurol 2019 09;78(9):854-864

Department of Pathology, Princess Margaret Hospital.

KLHL40-related nemaline myopathy is a severe autosomal recessive muscle disorder. The current study describes 4 cases of KLHL40-related nemaline myopathy in Hong Kong ethnic Chinese presenting within 3 years, which are confirmed with clinicopathologic features and genetic studies. The incidence is estimated to be at least 1 in 45 226 livebirths (at least 1 in 41 608 among ethnic Chinese livebirths) in Hong Kong. Hyponatremia appears to be another common feature in these patients. Salient histological features include nemaline bodies ranging from 200 to 500 nm in diameters on ultrastructural examination as well as negative KLHL40 immunohistochemistry; type II fiber predominance is obvious in 2 cases. We demonstrate the founder effect associated with genetic variant c.1516A>C (p.Thr506Pro) by polymorphic marker analysis, which revealed a 0.56-0.75-Mb or 0.41-0.78-cM shared haplotype encompassing the disease allele. The mutation is believed to have occurred around 412 generations ago or 6220 BCE, as estimated using DMLE+ and a formula described by Boehnke. We believe the founder variant might possibly underlie a sizable portion of nemaline myopathy in ethnic Chinese. Analysis of the KLHL40 gene may be considered as the first-tier testing of congenital myopathy in this ethnic group.
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http://dx.doi.org/10.1093/jnen/nlz056DOI Listing
September 2019

The role of human papillomavirus in head and neck squamous cell carcinoma: A case control study on a southern Chinese population.

J Med Virol 2016 May 3;88(5):877-87. Epub 2015 Nov 3.

Department of Microbiology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

HPV plays a role in the development of a portion of head and neck squamous cell carcinoma (HNSCC), but only limited information on its role in southern Chinese population is available. A multicenter case-control study was conducted. HPV type, viral integration, E6/7 mRNA expression status, and TP53 mutation were determined. A total of 228 HNSCC were recruited including 137 (60.1%) oral SCC, 34 (14.9%) oropharyngeal SCC, 31 (13.6%) laryngeal SCC, 21 (9.2%) hypopharyngeal SCC, and 5 (2.2%) lip and paranasal sinus SCC. High-risk HPV infection was found in 7.5% (17/228) of HNSCC, but only a small proportion of samples had evidence of viral integration (5.3%, 12/228) or E6/7 mRNA expression (4.4%, 10/228). HPV infection with oncogenic phenotype (integration and E6/7 mRNA expression) was significantly more common in oropharyngeal SCC than controls (9/34, 26.5% vs. 0/42, 0.0%, P < 0.001). Smoking showed a significant association with HNSCC, oropharyngeal SCC, and laryngeal SCC. TP53 mutation was associated with HNSCC (P < 0.001). Older age, TP53 mutation, and HPV16 infection with oncogenic phenotypes were independently associated factors for HNSCC with odds ratios of 1.03 (1.02-1.05), 3.38 (1.71-6.66), and 9.19 (1.13-74.68), respectively. High-risk HPV infection of head and neck mucosa is not uncommon in the Hong Kong population. This study found that 26-30% of oropharyngeal carcinoma was associated with HPV infection, mostly HPV16, and that smoking which predisposes to TP53 mutations was another important risk factor.
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http://dx.doi.org/10.1002/jmv.24405DOI Listing
May 2016

Myopericytoma in patients with AIDS: a new class of Epstein-Barr virus-associated tumor.

Am J Surg Pathol 2009 Nov;33(11):1666-72

Department of Pathology, Queen Elizabeth Hospital, Hong Kong, SAR China.

Myopericytoma is an uncommon, benign perivascular myoid cell tumor that occurs almost exclusively in somatic soft tissues. We report 2 cases occurring in patients with acquired immunodeficiency syndrome who show unusual clinical and biologic features. One patient presented with a bronchial mass and the other developed mass lesions of the tongue, vocal cord, and brain. Histologically, oval to plump spindly tumor cells with uniform nuclei and scanty cytoplasm formed sheets or cuffs around gaping or narrow vascular spaces. Focally, these areas merged into fascicles of more elongated cells with eosinophilic cytoplasm. The tumor cells were immunoreactive for actin but not desmin, and showed uniform labeling for Epstein-Barr virus (EBV) encoded RNAs on in-situ hybridization. Both patients were alive 5 years after incomplete excision of the lesions. In conjunction with another case reported in the literature, myopericytoma occurring in acquired immunodeficiency syndrome patients exhibits several features distinct from sporadic myopericytoma: presentation in anatomic sites other than somatic soft tissues, frequent presence of multifocal disease, and association with EBV. This tumor type therefore also broadens the spectrum of neoplasms associated with EBV.
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http://dx.doi.org/10.1097/PAS.0b013e3181aec307DOI Listing
November 2009

Lhermitte-Duclos disease associated with Cowden syndrome.

J Clin Neurosci 2007 Aug 7;14(8):801-5. Epub 2007 May 7.

Department of Neurosurgery, Queen Elizabeth Hospital, Kowloon, Hong Kong.

Lhermitte-Duclos disease or dysplastic gangliocytoma of the cerebellum, is a rare cerebellar lesion, which can cause mass effects in the posterior fossa. It may occur sporadically, or in association with Cowden syndrome. Cowden syndrome or multiple hamartoma-neoplasia syndrome, is an uncommon autosomal dominant condition characterized by mucocutaneous lesions and systemic malignancies. We report two patients with Lhermitte-Duclos disease and associated Cowden syndrome. The clinical, radiological and histopathological features and management strategies of this rare disease complex are discussed.
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http://dx.doi.org/10.1016/j.jocn.2006.06.007DOI Listing
August 2007

Pleomorphic xanthoastrocytoma: report of two cases and review of the prognostic factors.

J Clin Neurosci 2004 Feb;11(2):203-7

Department of Neurosurgery, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong.

Pleomorphic xanthoastrocytoma (PXA) is a superficially located, rare glial tumour first described in 1979. It affects young patients, who often present with seizures. The tumour has a relatively favourable prognosis, but 15-20% progress to malignancy. We describe two cases of PXA, both with benign features at presentation, one of which underwent anaplastic transformation. Surgery remains the mainstay of treatment. Factors influencing clinical outcome include extent of resection, and histological features such as mitotic index, necrosis and lymphocytic infiltration. The roles of radiotherapy and chemotherapy remain undefined. We advocate lifelong follow-up and establishment of a central registry in order to further the understanding of this infrequently encountered tumour.
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http://dx.doi.org/10.1016/j.jocn.2003.04.003DOI Listing
February 2004

Pigmented ependymoma with lipofuscin and neuromelanin production.

Arch Pathol Lab Med 2003 Jul;127(7):872-5

Department of Pathology, Queen Elizabeth Hospital, Hong Kong.

We report an unusual case of ependymoma with pigmentation, a phenomenon that has only been described in a few cases, to our knowledge. This tumor occurred in the fourth ventricle of a 45-year-old man. It showed the typical histologic appearance of ependymoma with perivascular pseudorosettes and rare ependymal rosettes. Some tumor cells contained brown cytoplasmic pigment, which was shown histochemically to represent a mixture of lipofuscin and neuromelanin. The pigment was positive for acid-fast and periodic acid-Schiff stains and was also focally positive for Masson-Fontana and Schmorl stains (bleached by pretreatment with potassium permanganate). In addition, some other tumor cells showed a signet ring morphology as a result of prominent intracytoplasmic vacuolation. Immunohistochemically, all the tumor cells expressed glial fibrillary acidic protein, and rare pigmented tumor cells also expressed HMB-45. Ultrastructural examination showed irregularly shaped heterogeneous electron-dense bodies corresponding to the pigment, and the cytoplasmic vacuoles were formed by dilatation of intracytoplasmic lumens lined by microvilli. Since lipofuscin production can occur in normal ependymal cells and neuromelanin has been suggested to be a melanized form of lipofuscin, it is not surprising that these 2 pigments can be found in ependymoma. In all the previously reported cases, the pigment was shown to represent melanin only. In our case, the HMB-45 positivity in rare tumor cells indicated that there might also be a minor melanin component in the pigment in addition to lipofuscin and neuromelanin.
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http://dx.doi.org/10.5858/2003-127-872-PEWLANDOI Listing
July 2003
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