Child with Deletion 9p Syndrome Presenting with Craniofacial Dysmorphism, Developmental Delay, and Multiple Congenital Malformations

A 4-month-old Sri Lankan male child case with a de novo terminal deletion in the p22 → pter region of chromosome 9 is described. The child presented with craniofacial dysmorphism, developmental delay, and congenital malformations in agreement with the consensus phenotype. A distinctive feature observed in this child was complete collapse of the left lung due to malformation of lung tissue. Cytogenetic studies confirmed terminal deletion of the short arm of chromosome 9 distal to band p22 [46,XY,del(9)(p22 → pter)]. This is the first reported case of a de novo deletion 9p syndrome associated with pulmonary hypoplasia. This finding contributes to the widening of the spectrum of phenotypic features associated with deletion 9p syndrome

Combined effect of CCND1 and COMT polymorphisms and increased breast cancer risk

<p>Abstract</p> <p>Background</p> <p>Estrogens are crucial tumorigenic hormones, which impact the cell growth and proliferation during breast cancer development. Estrogens are metabolized by a series of enzymes including COMT, which converts catechol estrogens into biologically non-hazardous methoxyestrogens. Several studies have also shown the relationship between estrogen and cell cycle progression through activation of CCND1 transcription.</p> <p>Methods</p> <p>In this study, we have investigated the independent and the combined effects of commonly occurring CCND1 (Pro241Pro, A870G) and COMT (Met108/158Val) polymorphisms to breast cancer risk in two independent Caucasian populations from Ontario (1228 breast cancer cases and 719 population controls) and Finland (728 breast cancer cases and 687 population controls). Both COMT and CCND1 polymorphisms have been previously shown to impact on the enzymatic activity of the coded proteins.</p> <p>Results</p> <p>Here, we have shown that the high enzymatic activity genotype of CCND1^High(AA) was associated with increased breast cancer risk in both the Ontario [OR: 1.3, 95%CI (1.0–1.69)] and the Finland sample [OR: 1.4, 95%CI (1.01–1.84)]. The heterozygous COMT^Medium(MetVal) and the high enzymatic activity of COMT^High(ValVal) genotype was also associated with breast cancer risk in Ontario cases, [OR: 1.3, 95%CI (1.07–1.68)] and [OR: 1.4, 95%CI (1.07–1.81)], respectively. However, there was neither a statistically significant association nor increased trend of breast cancer risk with COMT^High(ValVal) genotypes in the Finland cases [OR: 1.0, 95%CI (0.73–1.39)]. In the combined analysis, the higher activity alleles of the COMT and CCND1 is associated with increased breast cancer risk in both Ontario [OR: <b>2.22</b>, 95%CI (1.49–3.28)] and Finland [OR: <b>1.73</b>, 95%CI (1.08–2.78)] populations studied. The trend test was statistically significant in both the Ontario and Finland populations across the genotypes associated with increasing enzymatic activity.</p> <p>Conclusion</p> <p>Using two independent Caucasian populations, we have shown a stronger combined effect of the two commonly occurring CCND1 and COMT genotypes in the context of breast cancer predisposition.</p

Using global team science to identify genetic parkinson's disease worldwide.

No abstract available

Genotype and allele frequencies of the polymorphic methylenetetrahydrofolate reductase gene in Turkey

The polymorphic methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms C677T and A1298C cause mild hyperhomocysteinemia, not only in homozygotes for C677T, but also in compound heterozygotes for C677T/A1298C. The aim of this study was to determine allelic frequencies of the polymorphic MTHFR gene C677TA1298C. In this regard, we have investigated the allelic frequencies of C677T and A1298C polymorphisms of the MTHFR gene in 1684 randomized individuals around Turkey. DNA samples isolated from peripheral blood samples of randomized individuals were analysed. The study population consisted of 1004 females and 680 males. The frequency in Turkey of the C677T was 42.9%; of C677C, 47.4%; and of T677T, 9.6%. The frequency in Turkey of A1298C was 43.7%; of A1298A, 46.3%; and of C1298C, 10.0%. The allelic frequencies of the T allele of MTHFR 677 and the C allele of MTHFR 1298 were 33.34 and 33.16%, respectively. The frequency of C677T/A1298C compound heterozygosity is highest in Turkey (21.6%), as compared to Canada (15%), the United States (17%) and The Netherlands (20%). Copyright (C) 2004 John Wiley Sons, Ltd

Association of the C677T and A1298C polymorphisms in the 5,10 methylenetetrahydrofolate reductase gene in patients with migraine risk

Although controversial, diminished activity of 5,10 methylenetetrahydrofolate reductase (MTHFR), a regulatory enzyme of homocysteine metabolism, may predispose to migraine in Turkish people. In a case-control study, we determined the prevalence of two common MTHFR polymorphisms,C677T and A1298C, in 102 migraine patients (23 migraine with aura, 70 migraine without aura and nine with tension-type headache) and compared it to that of 136 healthy controls. The frequencies of the T allele of MTHFR677 and the C allele of MTHFR1298 were significantly higher in the total migraine population (33.82%, 33.82%) than in controls (25.38% and 24.26%), respectively. The genotypes T677T and C1298C were the only genotypes significantly associated with migraine (OR=5.702; 95% CI=1.184-27.457; P=0.015) and (OR=8.933; 95% CI=1.953-40.869; P=0.001), respectively). Individuals with migraine with aura with C1298C and C677C/C1298C genotypes were even more profoundly associated with migraine risk than others (OR=14.105; 95% CI=2.417-82.320; P=0.0001) and (OR=10.050; 95% CI=1.580-63.907; P=0.003), respectively. However individuals with migraine without aura with T677T and C1298C genotypes showed the same susceptibility (OR=7.444; 95% CI=1.503-36.863); P=0.005). Patients with C1298C and C677C/C1298C genotypes may also predispose to tension-type headache (OR=8.375; 95% CI=0.685-102.458); P=0.049). (C) 2003 Elsevier Science B.V. All rights reserved

Methylenetetrahydrofolate reductase gene polymorphisms in patients with schizophrenia

To investigate the role of methylenetetrahydrofolate reductase gene polymorphisms in schizophrenia, we analyzed the genotypes of MTHFR677 and MTHFR1298 of 130 schizophrenic patients and 226 controls, using a polymerase chain reaction restriction fragment length polymorphism method. The MTHFR T677 allele was significantly distributed (chi(2) = 7.900; P = 0.019), between schizophrenic cases and healthy controls. The T677T genotype was overrepresented in the schizophrenic patients (OR = 2.504; 95% CI = 1.276-4.915; 2 chi(2) = 7.477; P = 0.006). The T677T/A1298A, and C677T/C1298C compound genotypes were greater in the schizophrenic patients, (OR = 3.157; 95% CI = 1.522-6.545; chi(2) = 10.336; P = 0.001 and OR = 1.744; 95% CI = 0.108-28.121; chi(2) = 0.158; P = 0.691, respectively). The MTHFR T677 allele and T677T and T677T/A1298A genotypes are genetic risk factors for schizophrenia. (C) 2003 Elsevier B.V. All rights reserved