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C P Pang

Publications and source records attributed to C P Pang.

At least 37 records · Page 2Linked to original sources
PubMed2001

The miracle of microarray data analysis.

A report on the tenth Annual Bioinformatics and Genome Research meeting of the Cambridge Healthtech Institute's Beyond Genome 2001 series, San Francisco, USA, 17-19 June 2001.

Humans↗
PubMed2001

Genetic imbalances in pT2 breast cancers of southern Chinese women.

While much information has been reported on the genetic alterations in breast cancers of Caucasians, little is known about the Oriental populations where breast cancers currently rank the second most common neoplasm. As a first step toward understanding the underlying genetics changes in this population, we used comparative genomic hybridization (CGH) to the genome-wide analysis of forty pT2 tumors from patients of a racially homogenous population in southern China. A complex pattern of genetic alterations emerged with the commonest chromosomal gains identified on 1q (58%), 8q (55%), 11q13 (25%), 16p (28%), 17q (53%) and 20q (35%), and frequent losses on 8p (38%), 11q (28%), 13q (30%) and 18q (25%). When breast cancers with and without lymph-node metastasis were compared, a higher copy gain of 10p was identified in the node-positive group (P=.036). An overall increase in the average number of genetic aberrations was also identified in the late onset group (>45 years)(P=.042) with a higher incidence of genetic losses noted (P=.035). In particular, losses on 16q were detected in 30% of the late onset patients but none in the early onsets (P=0.049). In this study, we have illustrated the pattern of genetic changes in breast tumors of southern Chinese females. While frequent 1q, 8q, 17q and 20q gains, and common 8p and 13q deletions detected were consistent to those aberrations reported from the Caucasian populations, the difference in genetic changes associated in lymph-node metastasis and age of onset identified should provide the basis for additional investigations into the underlying tumorigenesis in the Oriental population.

Adult↗
PubMed2001

RP1 in Chinese: Eight novel variants and evidence that truncation of the extreme C-terminal does not cause retinitis pigmentosa.

Heterozygous truncating mutations in the RP1 gene cause approximately 7% of autosomal dominant retinitis pigmentosa (RP) cases. To examine the role of RP1 mutations in RP, we screened 101 unrelated Chinese RP patients (unselected for mode of inheritance) and 190 elderly normal control subjects for sequence changes in the coding exons for the 2156 amino acid RP1 protein. One patient had a mutation, thus RP1 mutations cause about 0.0% to 5.4% (95% confidence interval) of all RP among Chinese. The mutation was R677X, the most common found in Americans. Five other known sequence changes were found. In addition, nine novel sequence alterations were identified: 746G>A (R249H), 1437G>T (M479I), 2116G>C (G706R), 3024G>A (Q1008Q), 3188G>A (Q1063R), 5797C>T (R1933X), 6423A>G (I2141M), and the variants 6542C>T and 6676T>A, both in the 3' untranslated region. One control subject and three members of a non-RP family were heterozygous for R1933X, which is therefore likely to be a non-disease-causing variant. The most C-terminal truncation previously reported was due to Tyr1053 (1-bp del) and occurred in RP patients. Thus the presence of a normal level of at least part of RP1 between amino acids 1052 and 1933 appears necessary to prevent RP. Hum Mutat 17:436, 2001.

3' Untranslated Regions↗
PubMed2001

Indocyanine green staining and removal of internal limiting membrane in macular hole surgery: histology and outcome.

PURPOSE: To report the surgical technique, outcome, and histologic findings involving indocyanine green staining and removal of internal limiting membrane in primary macular hole surgery. METHODS: Prospectively, consecutive patients with idiopathic macular hole or myopic macular hole with retinal detachment were recruited. After pars plana vitrectomy and epiretinal membrane removal, the internal limiting membrane was stained and removed. The specimens were stained using hematoxylin and eosin and periodic acid-Schiff. Immunohistochemical staining was also performed for glial fibrillary acidic protein, vimentin, type I and type IV collagen, and actin. RESULTS: Among 10 patients (10 eyes) in the study, nine eyes had stage 3 or 4 macular hole. Four of them had chronic macular hole. The tenth patient had retinal detachment resulting from a myopic macular hole. Postoperatively, all cases had closure of macular hole without an elevated edge and the retina was attached. Seven patients had improvement of 2 or more Snellen lines, whereas visual acuity remained the same for the other three patients. In six eyes in which complete histologic examinations were feasible, internal limiting membrane was confirmed and two eyes also had a small amount of epiretinal membrane. Myofibrocytes in internal limiting membrane, either scattered or as a single layer, were found in three cases. CONCLUSIONS: Removal of indocyanine green--stained internal limiting membrane around idiopathic macular hole or myopic macular hole with retinal detachment is confirmed with histology and may contribute to macular hole closure and retinal reattachment.

Actins↗
PubMed2001

Prevalence of breast cancer predisposition gene mutations in Chinese women and guidelines for genetic testing.

BACKGROUND: Breast cancer is the most common cancer among Caucasian females. On average, 1 in 12 women will have breast cancer during their lifetime. There is a marked difference in breast cancer incidence in Chinese. In Hong Kong women, the lifetime risk is 1 in 29. BRCA1 and BRCA2 are high-penetrant cancer predisposition genes, but the prevalence and nature of mutations in these genes appear to be ethnic-specific. It is not clear if the differences in cancer incidence between Caucasians and Chinese are due to genetic or environmental factors. METHODS: In our investigation of BRCA1 mutations among Chinese female patients in Hong Kong, BRCA1 mutations were found in 3.8% (CI: 1.3-8.8%) of 130 breast cancer patients. The prevalence was higher in a separate group of 56 early onset patients, aged<45 years, (8%, CI: 2.2-19.2). Most of the mutations were different from those reported in Caucasians. A deletion 589delCT was found in three unrelated patients, which may represent a common mutation. Similar prevalence of mutations was reported in Taiwan and Singapore Chinese. Other low-penetrant cancer predisposition genes may be important in the pathogenesis of the majority of breast cancers. CONCLUSIONS: Although the epidemiology of breast cancer is different between Caucasians and Chinese, the prevalence of mutations in the high-penetrant cancer-predisposition gene of BRCA1 is comparable. It may indicate that the role of genetic contribution to breast cancer may be similar in the two ethnic groups and the difference in epidemiology may be contributed more heavily by environmental factors.

BRCA2 Protein↗
PubMed2001

Molecular diagnostics for retinitis pigmentosa.

BACKGROUND: At least 1 million people worldwide have retinitis pigmentosa (RP), making it relatively common among the inherited forms of blindness. Mutations in many genes may cause RP. The most common known mutation, Pro347Leu in rhodopsin, is found in no more than about 1% of unrelated patients, implying the impracticality of a diagnostic test which would screen only for a few, common mutation sites. CONCLUSIONS: Ongoing discovery and study of RP genes makes it feasible to consider a molecular diagnostic test which would screen coding regions of all known RP genes by a mutation detection method such as conformation-sensitive gel electrophoresis followed by sequencing. The parallel development of RP genetic knowledge and treatments such as gene therapy will make such tests both possible and necessary.

China↗
PubMed2001

All aboard the chip!

The Cambridge Healthtech Institute's Microarrays and Microchips conference was held in Tokyo, Japan, 4-5 June 2001.

Biotechnology↗
PubMed2001

Rhodopsin mutations in Chinese patients with retinitis pigmentosa.

AIM: To determine the pattern of rhodopsin mutations in Chinese retinitis pigmentosa (RP) patients. METHODS: The rhodopsin gene was examined in 101 RP patients and 190 controls from Hong Kong. RESULTS: Three coding changes were identified: Pro347Leu, Ala299Ser, and 5211delC. Each protein sequence alteration was found in one patient. Ala299Ser also existed in two controls. CONCLUSION: The C-terminal nonsense mutation may cause mis-sorting of rhodopsin protein. The finding of controls with Ala299Ser suggests this is only the third missense alteration reported that does not cause RP. The expected frequency of rhodopsin mutations in RP is <7% (2/101=2.0%, 95% confidence interval: 0.2%-7.0%).

Adult↗
PubMed2001

High-throughput conformation-sensitive gel electrophoresis for discovery of SNPs.

High-throughput screening for single nucleotide polymorphisms (SNPs) or mutations can be achieved by inexpensive technologies. We modified the original protocols of conformation-sensitive gel electrophoresis (CSGE) to increase throughput several fold to 1.3 samples/min, which is about five times faster than denaturing high-performance liquid chromatography (DHPLC). The modifications include decreasing the gel thickness, increasing the number of lanes to 96, and increasing the number of samples per lane to seven. This high-throughput CSGE method is fast, robust, and as simple as the original protocols. Together with a two-stage strategy for screening homozygotes and the replacement of ethidium bromide with SYBR Gold DNA dye staining, this protocol is a reliable and cost-effective alternative for laboratories that require high-throughput screening.

Heterozygote↗
PubMed2000

Apolipoprotein E isoforms in Alzheimer's disease pathology and etiology.

The apolipoprotein E (apoE) epsilon4 allele increases risk of Alzheimer's disease (AD), perhaps by accelerating plaque formation, or by impairing neuron repair. Considerable evidence supports both mechanisms. AD patients with epsilon4 have more and earlier amyloid deposits than do patients without epsilon4. The same is true of non-demented control subjects. In vitro, all apoE isoforms inhibit amyloid beta protein (Abeta) aggregation, but apoE4 less effectively than apoE3. Transgenic amyloid-producing mice expressing apoE3 or apoE4 develop less Abeta deposition than apoE knockout mice. These observations are consistent with an effect of apoE isoforms on Abeta aggregation in AD. ApoE is important for neurite maintenance since apoE knockout mice lose neurites and suffer behavioral deficits with aging or treatment with excitotoxins. ApoE4 mice show similar defects, but apoE3 mice are normal. AD patients with epsilon4 show more neuritic deficits than epsilon3 carriers. ApoE epsilon4 also worsens neurological impairment in head injury, stroke, and multiple sclerosis. Thus, apoE4 is less effective at neurite maintenance. Perhaps epsilon4 increases AD risk by both mechanisms: allowing amyloid deposition and failing to repair neurites. In either case, introducing apoE3 or apoE2 into the brain, for example by gene therapy or cell grafts, might delay AD progression.

Alzheimer Disease↗
PubMed2000

Roles for lipoprotein lipase in Alzheimer's disease: an association study.

Lipoprotein lipase (LPL) assists lipid transport by transferring lipids between lipoprotein particles and cells. LPL binds apolipoprotein E (apoE) lipoprotein particles and a major apoE receptor, low density lipoprotein receptor related protein (LRP). Because apoE and LRP polymorphisms alter Alzheimer's disease (AD) risk, and LPL itself is found in AD amyloid plaques, we examined whether LPL variants also affect AD risk. In case-control studies in the United States and Canada, the frequencies of two LPL alleles known to affect LPL enzymatic activity were measured in Caucasian AD or elderly normal (N) subjects. Pathologically confirmed subjects in both studies exhibited similar trends toward fewer 447Ter and more 291Ser alleles in AD. Combining results from both countries gave allele frequencies for 447Ter of 13.7% (26/190) in N and 9.4% (80/852) in AD (P = 0.10), and for 291Ser of 0.0% (0/184) in N and 1. 3% (8/636) in AD (P = 0.21). The trend appeared even greater for homozygous 447Ter subjects: 4.2% (4/95) of N vs. 1.4% (6/426) of AD (P = 0.09). These trends are consistent with a putative protective effect of 447Ter and causative effect of 291Ser on AD. Furthermore, brains of AD patients with 447Ter showed trends toward fewer plaques, tangles, and glia, and more neurons and cortical thickness than AD patients without 447Ter. Hippocampal plaques were significantly reduced. LPL might affect hippocampal function and thus dementia via its role as supplier of membrane components or antioxidants to neurons. Alternatively, LPL may play a part in plaque formation through its interaction with apoE and LRP.

Aged↗
PubMed2000

The alpha-synuclein gene and Parkinson disease in a Chinese population.

OBJECTIVE: To study the Ala53Thr and Ala30Pro mutations of the alpha-synuclein gene in a large number of Chinese patients with Parkinson disease (PD) as well as controls. METHODS: We recruited 183 Chinese patients with sporadic PD, 17 with younger-onset PD (onset age <50 years), and 7 with PD and a positive family history as well as 227 unaffected Chinese control subjects from the outpatient departments of 2 major hospitals in Hong Kong. All subjects were assessed for the the diagnosis of PD by a consultant neurologist or geriatrician. Subjects were interviewed with a standard questionnaire that also questioned for family history. Venous blood samples were obtained from the subjects and genomic DNA was extracted and studied for the presence of Ala53Thr mutation in exon 4 and Ala30Pro mutation in exon 3 of the alpha-synuclein gene using a polymerase chain reaction restriction fragment length polymorphism method. RESULTS: None of the Chinese PD patients or controls had either the Ala53Thr (exon 4) or Ala30Pro (exon 3) mutation of the alpha-synuclein gene. CONCLUSION: We failed to discover Ala53Thr or Ala30Pro mutations in a large number of Chinese patients with PD and control subjects, adding to the emerging consensus that variations in the alpha-synuclein gene are associated with PD in few families worldwide.

Alleles↗