A novel homozygous mutation of GJC2 derived from maternal uniparental disomy in a female patient with Pelizaeus-Merzbacher-like disease.

J Neurol Sci. 2013 May 16;

Authors: Shimojima K, Tanaka R, Shimada S, Sangu N, Nakayama J, Iwasaki N, Yamamoto T

Abstract
Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating disorder of the central nervous system characterized by nystagmus, motor developmental delay, ataxia, and progressive spasticity. The gap junction protein gamma-2 gene (GJC2), encoding the gap junction protein connexin 47, is one of the genes responsible for this condition. In this study, a novel homozygous mutation in GJC2 (c.746C>G; p.P249R) was identified in a 21-year-old female patient with PMLD. Although her mother was a carrier of this mutation, the Mendelian inheritance pattern could not be determined because the paternal sample was unavailable. Alternatively, chromosomal microarray testing together with single nucleotide polymorphism typing (CGH+SNP) was performed to determine the gene copy number and analyze the haplotype in the 1q42.13 region in which GJC2 is located. The result showed no deletion, but the GJC2 region was involved in the loss-of-heterozygosity region. Furthermore, haplotype of chromosome 1, in which GJC2 is located, revealed that both copies of chromosome 1 were derived from the patient's mother, indicating maternal uniparental disomy of chromosome 1. This study showed the advantage of the SNP genotyping microarray for detecting the origin of the mutation.

PMID: 23684670 [PubMed - as supplied by publisher]

Pregnancy outcomes amongst thalassemia traits.

Arch Gynecol Obstet. 2013 May 17;

Authors: Hanprasertpong T, Kor-Anantakul O, Leetanaporn R, Suntharasaj T, Suwanrath C, Pruksanusak N, Pranpanus S

Abstract
OBJECTIVE: To compare the pregnancy outcome between pregnancies affected and not affected by thalassemia trait. METHODS: A retrospective case-control cohort study was conducted on singleton pregnant women who attended antenatal care and delivered at Songklanagarind Hospital. All of the participating thalassemia trait pregnant women were diagnosed based on hemoglobin typing and/or DNA analysis. A ratio of around 1-1 was used to compare their pregnancy outcomes with normal pregnant women. RESULTS: Seven hundred thirty-nine thalassemia trait and 799 normal pregnant women were included in the study. All of the women were Thai nationals living in the Southern Region of Thailand and nearly all of them had spontaneously conceived. Maternal complication rates of gestational diabetes, preterm birth, antepartum bleeding, postpartum bleeding, shoulder dystocia and puerperal morbidity, and the rates of neonatal complications: macrosomia, fetal weight <2,000 g, intrauterine growth restriction (IUGR), stillbirth, low Apgar score (<7) at 1 and 5 min and NICU admission, were not significantly different between the two groups. The rate of pre-eclampsia, however, was significantly different, with RRs of 1.73 (CI 1.01-3.00). CONCLUSION: The thalassemia trait condition did not affect the risk of gestational diabetes, postpartum hemorrhage, stillbirth, preterm birth and puerperal morbidity. However, pre-eclampsia should be warranted especially among nulliparous and high-BMI pregnant women.

PMID: 23681496 [PubMed - as supplied by publisher]

BRCA1 Polymorphisms and Breast Cancer Epidemiology in the Western New York Exposures and Breast Cancer (WEB) Study.

Genet Epidemiol. 2013 May 14;

Authors: Ricks-Santi LJ, Nie J, Marian C, Ochs-Balcom HM, Trevisan M, Edge SB, Freudenheim JL, Shields PG

Abstract
Results of studies for the association of BRCA1 genotypes and haplotypes with sporadic breast cancer have been inconsistent. Therefore, a candidate single nucleotide polymorphism (SNP) approach was used in a breast cancer case-control study to explore genotypes and haplotypes that have the potential to affect protein functions or levels. In a breast cancer case-control study, genotyping of BRCA1 polymorphisms Q356R, D693N, and E1038G was performed on 1,005 cases and 1,765 controls. Unconditional, polytomous logistic regression and χ(2) -tests were used to examine the associations of breast cancer with genotypes and haplotypes. In addition, interactions between genotype and smoking, benign breast disease, family history of breast cancer, body mass index (BMI), alcohol consumption, and hormonal risk factors, hormone receptor status, and breast cancer pathology were calculated also using logistic regression and χ(2) . Although sporadic breast cancer was not associated with BRCA1 genotypes or haplotypes overall or by menopausal status, there was evidence of an interaction between the E1038G BRCA1 genotype, smoking, and BMI among premenopausal women (P for interaction = 0.01 and 0.045, respectively) and between E1038G and D693N BRCA1 genotypes and hormone therapy use among postmenopausal women (P for interaction = 0.01 and 0.02, respectively). There were no other associations found between BRCA1 genotypes and stage, histological grade, or nuclear grade. However, the D693N SNP was associated with the risk of triple negative breast cancer (odds ratio = 2.31 95% confidence interval 1.08-4.93). The BRCA1 variants studied may play a role in the etiology of triple negative breast cancer and may interact with environmental factors such as hormone therapy or smoking and increase sporadic breast cancer risk.

PMID: 23674270 [PubMed - as supplied by publisher]

Polymorphism in the promoter region of the Toll-Like Receptor 9 gene and cervical human papillomavirus infection.

J Gen Virol. 2013 May 15;

Authors: Oliveira LB, Louvanto K, Ramanakumar AV, Franco EL, Villa LL

Abstract
Polymorphism in the Toll-like Receptor (TLR) 9 gene has been shown to have a significant role in some diseases; however, little is known about its possible role in the natural history of HPV infections. We investigated the association between a single nucleotide polymorphism (SNP) (rs5743836) in the promoter region of the TLR9 (T-1237C) and type specific HPV infections. Specimens were derived from a cohort of 2462 women enrolled in the Ludwig-McGill Cohort Study. We randomly selected 500 women who had a cervical HPV infection detected at least once during the study as cases. We defined two control groups: 1) a random sample of 300 women who always tested HPV negative and 2) a sample of 234 women who were always HPV negative but had a minimum of 10 visits during the study. TLR9 genotyping was performed using bidirectional PCR amplification of specific alleles. Irrespective of group, the wild-type homozygous TLR9 genotype (TT) was the most common form, followed by the heterozygous (TC) and the mutant homozygous (CC) forms. There were no consistent associations between polymorphism and infection risk, either overall, by type, or by species. Likewise, there were no consistently significant associations between polymorphism and HPV clearance or persistence. We conclude that this polymorphism in the promoter region of TLR9 gene does not seem to have a mediating role in the natural history of the HPV infection.

PMID: 23677790 [PubMed - as supplied by publisher]