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Journal Article 2015; 36(5): 511-514 PubMed PMID: 26707053 Citation  Keywords:  ACTH-Secreting Pituitary Adenoma:genetics, Adenoma:genetics, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor:genetics, Cohort Studies, Electrophoresis, Capillary, Female, Growth Hormone-Secreting Pituitary Adenoma:genetics, Humans, Male, Microsatellite .   

OBJECTIVE: Mutator phenotypes with microsatellite instability (MSI) are observed in a subset of solid tumors including those localized in the brain. MSI arises from impaired DNA mismatch repair. It can be a potential marker of resistance to radiation and chemotherapy, as demonstrated for several cancer types. Our study aims are to investigate MSI incidence in pituitary adenomas (PA) with a currently recommended methodology.

METHODS: DNA was obtained from 107 patients with PA of which 83 adenomas were nonfunctioning, 13 somatotrophic, 9 lactotrophic and 2 corticotrophic. These were examined for MSI status by PCR and capillary electrophoresis using five quasimonomorphic microsatellite markers: BAT25, BAT26, NR21, NR24 and NR27; in accordance to current Bethesda guidelines.

RESULTS AND CONCLUSION: No microsatellite instability was detected in the tumor samples thus implying the lack of any clinical usefulness of MSI testing in PA cases....

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Journal Article 2010; 31(4): 549-552 PubMed PMID: 20802447 Citation  Keywords:  Aged, Aged, 80 and over, Alleles, Czech Republic, Essential Tremor:genetics, Female, Gene Frequency, Genetic Association Studies, Genetic Heterogeneity, Genetic Loci, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Male, Microsatellite Re.   

OBJECTIVES: Essential tremor (ET) is one of the most common neurological movement disorders. In more than half of the cases, ET is inherited in an autosomal dominant manner, but no causative ET gene has been identified. However, several candidate loci have been reported, including the ETM2 locus that was originally found in a large American family of Czech descent.

METHODS: To ascertain the association with ETM2, we performed a genetic analysis of three polymorphic loci, etm1231, etm1234, and etm1240, located within the ETM2 candidate region in 61 Czech patients with a family history of ET and 68 healthy controls.

RESULTS: The allele frequencies were not significantly different between the patients and the controls, and we did not observe any haplotype specifically associated with ET.

CONCLUSIONS: This is the first report on the genetics of familial essential tremor in Czech patients. Our findings provide further evidence of genetic heterogeneity for ET....

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Journal Article 2010; 31(3): 370-374 PubMed PMID: 20588246 Citation  Keywords:  Adult, Aromatase:genetics, Asian Continental Ancestry Group:genetics, Female, Genetic Association Studies, Humans, Microsatellite Repeats, Polycystic Ovary Syndrome:genetics, Polymorphism, Genetic,.   

OBJECTIVE: Evidence indicates that the CYP19 gene is a positional and functional candidate for genetic study in polycystic ovarian syndrome (PCOS). The present study aims to evaluate the association between tetranucleotide TTTA repeat polymorphism in the CYP19 gene and PCOS among Han Chinese women.

METHODS: Clinical materials employed in this study consist of 123 patients with PCOS and 113 healthy controls. The CYP19 tetranucleotide TTTA repeat polymorphism was genotyped with a protocol of PCR and fluorescent capillary electrophoresis.

RESULTS: Common allele of the CYP19 tetranucleotide TTTA repeat polymorphism in this population of Han Chinese women was 11R. The frequency of 11R in PCOS was lower than in the control subjects (34.55% vs 42.92%, p=0.046). The carriers with allele 11R in PCOS had decreased CHO (5.00+/-0.63 vs 6.14+/-0.85 mmol/L, p=0.012). The carriers with allele 7R-TCT in PCOS had increased CHO (5.96+/-0.83 vs 5.08+/-0.65 mmol/L, p=0.027) and LDL (5.11+/-0.77 vs 4.31+/-0.66 mmol/L, p=0.014) compared to the patients carrying other alleles.

CONCLUSIONS: The most common allele of the tetranucleotide TTTA repeat polymorphism in the forth intron of CYP19 gene in Han Chinese women is 11R, which was different with the previous study in European Caucasians. Allele 11R may be associated with PCOS in the population of Han Chinese women, and it may refrain from the hypercholesteremia of PCOS. Allele 7R-TCT may be related to the lipid metabolism of PCOS. This CYP19 tetranucleotide TTTA repeat polymorphism is an ethnic and racial variant and moderately contributes to the pathogenesis of PCOS in the population of Han Chinese women....

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Journal Article 2009; 30(1): 56-60 PubMed PMID: 19300392 Citation  Keywords:  Adult, Body Mass Index, Case-Control Studies, China, Cholesterol Side-Chain Cleavage Enzyme:genetics, Female, Gene Frequency, Genetic Linkage, Genetic Predisposition to Disease, Genotype, Humans, Microsatellite Repeats:genetics, Polycystic Ovary Syndrome:.   

: Evidence indicates that CYP11alpha is a positional and functional candidate for genetic study in polycystic ovarian syndrome (PCOS). In the present study, we have evaluated the association between the CYP11alpha promoter pentannucleotide (tttta)n polymorphism and PCOS among Han Chinese women. Subjects include 125 patients with PCOS and 121 healthy controls, and all were Han Chinese women. Clinical characteristics of patients with PCOS and control subjects were examined according to the Rotterdam consensus criteria. The CYP11alpha promoter pentannucleotide (tttta)n polymorphism was genotyped with PCR and fluorescent capillary electrophoresis protocol. Results indicate that common alleles of the CYP11alpha promoter pentannucleotide (tttta)n polymorphism in this population of Han Chinese women were P4, P6 and P8, and allele P6 was the most common one. Frequencies of those three common alleles between PCOS cases and controls (24.8, 65.6, 6.8% and 23.6, 65.7, 9.9%, respectively) were similar. No significant allelic association of this polymorphism with PCOS was found. However, the carriers with allele P6 among patients with PCOS had increased WHR (0.85+/-0.05 vs 0.82+/-0.08, P=0.039) and decreased AUCG (9.5+/-2.1 vs 11.4+/-2.8, P=0.021) compared to the patients carrying other alleles. Therefore, the most common allele of the CYP11alpha promoter pentannucleotide (tttta)n polymorphism in the population of Han Chinese women is P6, while the most common allele in European Caucasians, as previously reported, is P4. This polymorphism is an ethnic and racial variant, and may have the risk susceptibility in abnormal metabolism of patients with PCOS in Han Chinese women....

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Case Reports 2006; 27(5): 579-585 PubMed PMID: 17159828 Citation  Keywords:  Child, Preschool, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 8, Cytogenetic Analysis, DNA Methylation, Female, Humans, In Situ Hybridization, Fluorescence, Microsatellite Repeats, Prader-Willi Syndrome:genetics, Translocation, Genetic, Uniparen.   

OBJECTIVES: In contrast to most human autosomal genes which are expressed biallelically, the expression of imprinted genes depends on the parental origin of the allele. Prader-Willi syndrome is a neurobehavioral disorder in which the expression of active paternal alleles of imprinted genes from chromosomal region 15q11-q13 is abolished by deletions, maternal uniparental disomy or imprinting defects. We report an unusual case of maternal uniparental disomy of chromosome 15 due to a balanced translocation t(8;15)(q24.1;q21.2) leading to Prader-Willi syndrome in a 3-year-old girl.

METHODS AND RESULTS: Cytogenetic investigation revealed a balanced translocation t(8;15)(q24.1;q21.2) in the patient and subsequently also in her unaffected mother. Fluorescence in situ hybridization analysis did not reveal any deletion of the PWS critical region, but methylation analysis of the SNRPN gene showed an abnormal methylation pattern indicating the absence of paternal chromosome 15. Microsatellite analysis of multiple loci and methylation-specific MLPA analysis confirmed maternal uniparental heterodisomy of chromosome 15 as the cause of PWS in the patient.

CONCLUSIONS: This example emphasizes the importance of uniparental disomy testing in pregnancies of carriers of chromosomal aberrations with participation of chromosomes carrying imprinted genes involved in human diseases....

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Journal Article 2005; 26(5): 521-525 PubMed PMID: 16264407 Citation  Keywords:  Adult, Aged, Aging:physiology, Carcinoma, Papillary:genetics, Chromosomes:genetics, Genetic Markers, Humans, Loss of Heterozygosity:genetics, Microsatellite Repeats, Middle Aged, Protein-Tyrosine Kinases:genetics, RNA, Messenger:biosynthesis, Reverse Tran.   

OBJECTIVES: The aim of the study was to establish the LOH frequency of selected polymorphic markers in different histological types of thyroid tumors: 18 colloid goiters (CG), five follicular adenomas (FA), nine follicular carcinomas (FTC), 40 papillary carcinomas (PTC), and one anaplastic carcinoma (ATC). For PTC, tumors negative for RET/PTC rearrangements were preferred.

METHODS: LOH studies were performed using 14 highly polymorphic markers previously described as frequently lost in thyroid tumors.

RESULTS: In 20 cases (27%) the loss of at least one marker was found. No difference between the frequency of the LOH in FTC and PTC tumors was revealed (33% v. 33%). No differences between histopathological subtypes of PTC in LOH were found. Papillary thyroid carcinomas showed a tendency to higher LOH frequency from patients older than 45 years of age compared to younger ones (9/23 v. 4/17) although it was not statistically significant.

CONCLUSIONS: We conclude that papillary thyroid cancers, particularly those diagnosed in patients older than 45 years of age, do exhibit LOH at least with the same frequency as follicular cancers. This increased number of LOH events may contribute to the clinical aggressiveness of cancer in older patients....

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