Maternal periconceptional alcohol consumption and gastroschisis in the National Birth Defects Prevention Study, 1997–2011

Background: Gastroschisis is particularly prevalent among offspring of young women and has increased over recent decades. Although previous studies suggest that maternal alcohol consumption is associated with increased gastroschisis risk, none have explored whether maternal age modifies that association. Objective: The objective of the study was to evaluate associations between self-reported maternal periconceptional alcohol consumption (1 month prior through the third month after conception) and risk of gastroschisis among offspring, by maternal age. Methods: We used data from the National Birth Defects Prevention Study (NBDPS), a multi-site population-based case-control study. The analysis included 1450 gastroschisis cases and 11,829 unaffected liveborn controls delivered during 1997–2011 in ten US states. We estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the individual and joint effects of alcohol consumption and young maternal age at delivery (<25 years vs ≥25 years) on gastroschisis risk. We estimated the relative excess risk due to interaction (RERI) to quantify additive interaction. Results: Periconceptional alcohol consumption was common regardless of maternal age (women <25 years: cases 38.8%, controls 29.3%; women ≥25: cases 43.5%, controls 39.5%). Compared with women ≥25 years who did not consume alcohol, we observed increased risk of gastroschisis among women <25 years, with higher estimates among those who consumed alcohol (women <25 years who did not consume alcohol. aOR 5.90, 95% CI 4.89, 7.11; women <25 years who did consume alcohol: aOR 8.21, 95% CI 6.69, 10.07). Alcohol consumption among women ≥25 years was not associated with gastroschisis (aOR 1.12, 95% CI 0.88, 1.42). This suggests super-additive interaction between alcohol consumption and maternal age (RERI −2.19, 95% CI 1.02, 3.36). Conclusions: Periconceptional alcohol consumption may disproportionately increase risk of gastroschisis among young mothers. Our findings support public health recommendations to abstain from alcohol consumption during pregnancy

Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia Keratitis-Ichthyosis-Deafness syndrome.

Keratitis-ichthyosis-deafness syndrome (KID) is a rare ectodermal dysplasia characterized by vascularizing keratitis, profound sensorineural hearing loss (SNHL), and progressive erythrokeratoderma, a clinical triad that indicates a failure in development and differentiation of multiple stratifying epithelia. Here, we provide compelling evidence that KID is caused by heterozygous missense mutations in the connexin-26 gene, GJB2. In each of 10 patients with KID, we identified a point mutation leading to substitution of conserved residues in the cytoplasmic amino terminus or first extracellular domain of Cx26. One of these mutations was detected in six unrelated sporadic case subjects and also segregated in one family with vertical transmission of KID. These results indicate the presence of a common, recurrent mutation and establish its autosomal dominant nature. Cx26 and the closely related Cx30 showed differential expression in epidermal, adnexal, and corneal epithelia but were not significantly altered in lesional skin. However, mutant Cx26 was incapable of inducing intercellular coupling in vitro, which indicates its functional impairment. Our data reveal striking genotype-phenotype correlations and demonstrate that dominant GJB2 mutations can disturb the gap junction system of one or several ectodermal epithelia, thereby producing multiple phenotypes: nonsyndromic SNHL, syndromic SNHL with palmoplantar keratoderma, and KID. Decreased host defense and increased carcinogenic potential in KID illustrate that gap junction communication plays not only a crucial role in epithelial homeostasis and differentiation but also in immune response and epidermal carcinogenesis

Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia.

Item does not contain fulltextGap junctions are assemblies of intercellular channels that regulate a variety of physiologic and developmental processes through the exchange of small ions and signaling molecules. These channels consist of connexin family proteins that allow for diversity of channel composition and conductance properties. The human connexin 43 gene, or GJA1, is located at human chromosome 6q22-q23 within the candidate region for the oculodentodigital dysplasia locus. This autosomal dominant syndrome presents with craniofacial (ocular, nasal, and dental) and limb dysmorphisms, spastic paraplegia, and neurodegeneration. Syndactyly type III and conductive deafness can occur in some cases, and cardiac abnormalities are observed in rare instances. We found mutations in the GJA1 gene in all 17 families with oculodentodigital dysplasia that we screened. Sixteen different missense mutations and one codon duplication were detected. These mutations may cause misassembly of channels or alter channel conduction properties. Expression patterns and phenotypic features of gja1 animal mutants, reported elsewhere, are compatible with the pleiotropic clinical presentation of oculodentodigital dysplasia

Joint testing of genotypic and gene-environment interaction identified novel association for BMP4 with non-syndromic CL/P in an asian population using data from an International Cleft Consortium

10.1371/journal.pone.0109038PLoS ONE910e10903

Supplementary Material for: Genetic and Lifestyle Causal Beliefs about Obesity and Associated Diseases among Ethnically Diverse Patients: A Structured Interview Study

<b><i>Background:</i></b> New genetic associations with obesity are rapidly being discovered. People's causal beliefs about obesity may influence their obesity-related behaviors. Little is known about genetic compared to lifestyle causal beliefs regarding obesity, and obesity-related diseases, among minority populations. This study examined genetic and lifestyle causal beliefs about obesity and 3 obesity-related diseases among a low-income, ethnically diverse patient sample. <b><i>Methods:</i></b> Structured interviews were conducted with patients attending an inner-city hospital outpatient clinic. Participants (n = 205) were asked how much they agreed that genetics influence the risk of obesity, type 2 diabetes, heart disease, and cancer. Similar questions were asked regarding lifestyle causal beliefs (overeating, eating certain types of food, chemicals in food, not exercising, smoking). In this study, 48% of participants were non-Hispanic Black, 29% Hispanic and 10% non-Hispanic White. <b><i>Results:</i></b> Over two-thirds (69%) of participants believed genetics cause obesity ‘some' or ‘a lot', compared to 82% for type 2 diabetes, 79% for heart disease and 75% for cancer. Participants who held genetic causal beliefs about obesity held more lifestyle causal beliefs in total than those who did not hold genetic causal beliefs about obesity (4.0 vs. 3.7 lifestyle causal beliefs, respectively, possible range 0-5, p = 0.025). There were few associations between causal beliefs and sociodemographic characteristics. <b><i>Conclusions:</i></b> Higher beliefs in genetic causation of obesity and related diseases are not automatically associated with decreased lifestyle beliefs. Future research efforts are needed to determine whether public health messages aimed at reducing obesity and its consequences in racially and ethnically diverse urban communities may benefit from incorporating an acknowledgement of the role of genetics in these conditions

ROR2 gene is associated with risk of non-syndromic cleft palate in an Asian population

10.3760/cma.j.issn.0366-6999.2012.03.014Chinese Medical Journal1253476-48