Long term follow up of a woman with classic form of Ehlers-Danlos syndrome associated with rare manifestations and review of the literature.

We present the case of a 46 year-old woman with the classic type of Ehlers-Danlos syndrome who developed the rare manifestations of colon diverticula and mitral valve prolapse. We emphasize on clinical features and complications associated to this type of the syndrome, which gradually developed in our patient. A review of the literature referring to the epidemiology, molecular basis and manifestations of the classic type Ehlers-Danlos syndrome is also discussed.

Unilateral microtia in an infant with trisomy 18 mosaicism.

Trisomy 18 is the second most frequent autosomal aneuploidy, after Down's syndrome, in humans. It causes severe congenital abnormalities and mental retardation although phenotypic features, clinical manifestations and prognosis vary occasionally. In cases oftrisomy 18 mosaicism, as in every chromosomal mosaicism, the spectrum of clinical characteristics extends from pathological to almost normal. We report a 9 months old female infant who has been referred to the Genetics Department for evaluation because of unilateral severe microtia, aplasia of mastoid abscess and hemifacial palsy and inlet type intraventricular defect with pulmonary hypertension. Chromosomal investigation revealed a mosaic trisomy 18 [46,XX/47,XX+18] in proportion of 52% and 48% respectively. Microtia/anotia is present in 1.46-4.36/10,000 live births in the general population while the combination of microtia/anotia with trisomy 18 has been reported in very few cases in the relevant bibliography.

Association of repeat polymorphisms in the estrogen receptors alpha, beta (ESR1, ESR2) and androgen receptor (AR) genes with the occurrence of breast cancer.

Genetic variation in genes involved in estrogen biosynthesis, metabolism and signal transduction have been suggested to play a role in breast cancer. To determine the possible contribution of genetic variation in the ESR1 (ER-alpha), ESR2 (ER-beta) and AR genes in breast cancer risk the -1174(TA)(7-27), c. 1092+3607(CA)(10-26) and c. 172(CAG)(6-40) repeat variants were studied in a case-control study of 79 women with sporadic breast cancer and 155 controls. No significant difference was observed in the frequency distribution of -1174(TA)(7-27) in the ESR1 gene between patients and controls, while a significant difference was observed for repeat polymorphisms c. 1092+3607(CA)(10-26) in the ESR2 gene and c. 172(CAG)(6-40) in the AR gene (p0.0001). A significantly decreased odds ratio (OR) for breast cancer risk was observed in individuals having the LL and the SL genotypes for both the ESR2 (OR=0.010, 95% CI 0.003-0.036, p<0.001; OR=0.013, 95% CI 0.004-0.040, p<0.0001, respectively) and the AR gene (OR=0.040, 95% CI 0.011-0.138, p<0.0001; OR=0.189, 95% CI 0.10-0.359, p<0.0001, respectively), compared to SS genotype. The protective effect of these genotypes remained evident even after adjustment for various risk factors (BMI, age, age at menarche and menopause, family history). In conclusion, an association for breast cancer risk between short (SS) alleles for the repeat variants of the ESR2 and AR genes was found in women of Greek descent.

Steroid hormones polymorphisms and cholelithiasis in Greek population.

BACKGROUND: Genetic variation in genes involved in steroid biosynthesis, metabolism and signal transduction have been suggested to play a role in gallstone disease. METHODS: To elucidate the possible role of genetic variation in the estrogen receptors alpha and beta (ER-alpha, ER-beta) and androgen receptor (AR) genes in breast cancer risk, the -1174(TA)n, c.1092+3607(CA)(n) and c.172(CAG)n repeat polymorphisms of the three genes were studied. A case-control cohort of 99 patients with cholelithiasis and 179 controls were used. RESULTS: No significant difference was observed in the frequency distribution of -1174(TA)(0-26) in the ER-alpha gene between patients and controls, while a significant difference was observed in the frequency distribution of repeat polymorphism c.1092+3607(CA)5-27 and c.172(CAG)5-32 in the ER-beta gene and AR gene, respectively (P< or =0.001 and P=0.05, respectively). A significant difference was observed in the repeat genotype distribution (SS, SL, LL) in the (CA)n of the ER-beta gene (P<0.0001) and in the (CAG)n of the AR gene (P< or =0.0001). A significantly decreased odds ratio for cholelithiasis risk was observed in individuals having the SL and LL genotype for ER-beta gene compared with SS genotype (OR=0.212; 95% CI 0.105-0.426; P<0.0001 and OR=0.042; 95% CI 0.018-0.097, respectively) and LL genotype for AR gene (OR=0.622; 95% CI 0.345-1.121; P=0.114 and OR=0.287; 95% CI 0.151-0.543, P<0.0001, respectively). This protective effect of SL and LL genotypes for ER-beta and LL for AR gene remained evident (P<0.0001 for all of them) even after adjustment for various risk factors. CONCLUSIONS: In conclusion an association for cholelithiasis risk between short alleles for both c.1092+3607(CA)5-27 and c.172(CAG)5-32 repeat polymorphisms of the ER-beta and AR was found in individuals of Greek descent.

Interleukin-10G and interleukin-10R microsatellite polymorphisms and osteoarthritis of the knee.

OBJECTIVE: To clarify and evaluate the possible role of interleukin-10G (IL-10G) and interleukin-10R (IL-10R) microsatellite polymorphisms of IL-10 gene in knee osteoarthritis (OA). METHODS: This was a case-control study. Our population consisted of 132 patients with primary knee osteoarthritis who had undergone total knee replacement (TKR) and 165 unaffected controls. Peripheral blood was used to extract genomic DNA and the IL-10G and IL-10R polymorphisms were examined by a polymerase chain reaction (PCR)-based method and were analyzed using an automated DNA analysis method. RESULTS: A significant difference in the genotype distribution between OA individuals and controls was observed for IL-10G gene. Individuals with LL genotype were found to have almost 4 times greater possibility for knee OA than the ones with SS genotype (p = 0.001). OA patients had a significantly higher mean number of CA repeats for IL-10G gene than controls (p = 0.007). No significant differences in allelic frequencies between OA patients and controls were found for IL-10R gene. CONCLUSION: An association between IL-10G microsatellite polymorphisms and idiopathic knee OA was found in subjects of Greek descent.

Association of repeat polymorphisms in the estrogen receptors alpha, beta, and androgen receptor genes with knee osteoarthritis.

Genetic factors have been shown to play an important role in the etiology of osteoarthritis (OA). To elucidate the possible role of genetic variation in the estrogen receptors alpha and beta (ER-alpha, ER-beta) and androgen receptor (AR) genes with knee OA, the -1174(TA)(n), c.1092+3607(CA)(n), and c.172(CAG)(n) repeat polymorphisms of ER-alpha, ER-beta, and AR genes were studied. A case-control cohort of 158 patients with idiopathic knee OA and 193 controls were used. A significant difference was observed in the frequency distribution of -1174(TA)(9-25) and c.1092+3607(CA)(13-27) repeat polymorphisms of the ER-alpha and ER-beta genes between OA patients and controls (p<0.005 and p<0.0001, respectively). A significantly increased odds ratio (OR) for knee OA was observed in individuals having long alleles (LL) genotype for ER-alpha gene and LL and one short and one long allele (SL) genotypes for ER-beta gene compared to individuals with the short alleles (SS) genotype (95% CI 1.03-3.5; p=0.04 and CI 2.4-8.3 and 2.5-7.5; p < 0.001, respectively). When ORs were adjusted for various risk factors, it was observed that women with LL genotypes for ER-beta and AR genes showed significantly increased risk for OA development (p=0.002 and 0.001). An association between c.1092+3607(CA)(13-27) and c.172(CAG)(8-34) repeat polymorphisms of the ER-beta and AR genes and knee OA was found in individuals of Greek descent.