Prevalence and audiological features in carriers of GJB2 mutations, c.35delG and c.101T>C (p.M34T), in a UK population study

OBJECTIVES: To determine the carrier rate of the GJB2 mutation c.35delG and c.101T>C in a UK population study; to determine whether carriers of the mutation had worse hearing or otoacoustic emissions compared to non-carriers. DESIGN: Prospective cohort study. SETTING: University of Bristol, UK. PARTICIPANTS: Children in the Avon Longitudinal Study of Parents and Children. 9202 were successfully genotyped for the c.35delG mutation and c.101>T and classified as either carriers or non-carriers. OUTCOME MEASURES: Hearing thresholds at age 7, 9 and 11 years and otoacoustic emissions at age 9 and 11. RESULTS: The carrier frequency of the c.35delG mutation was 1.36% (95% CI 1.13 to 1.62) and c.101T>C was 2.69% (95% CI 2.37 to 3.05). Carriers of c.35delG and c.101T>C had worse hearing than non-carriers at the extra-high frequency of 16 kHz. The mean difference in hearing at age 7 for the c.35delG mutation was 8.53 dB (95% CI 2.99, 14.07) and 12.57 dB at age 9 (95% CI 8.10, 17.04). The mean difference for c.101T>C at age 7 was 3.25 dB (95% CI -0.25 to 6.75) and 7.61 dB (95% CI 4.26 to 10.96) at age 9. Otoacoustic emissions were smaller in the c.35delG mutation carrier group: at 4 kHz the mean difference was -4.95 dB (95% CI -6.70 to -3.21) at age 9 and -3.94 dB (95% CI -5.78 to -2.10) at age 11. There was weak evidence for differences in otoacoustic emissions amplitude for c.101T>C carriers. CONCLUSION: Carriers of the c.35delG mutation and c.101T>C have worse extra-high-frequency hearing than non-carriers. This may be a predictor for changes in lower-frequency hearing in adulthood. The milder effects observed in carriers of c.101T>C are in keeping with its classification as a mutation causing mild/moderate hearing loss in homozygosity or compound heterozygosity

Prenatal and Early Life Exposure to Stressful Life Events and Risk of Autism Spectrum Disorders: Population-Based Studies in Sweden and England

Background and Aim Exposure to stressful life events during pregnancy has been suggested as a potential risk factor for offspring Autism Spectrum Disorders (ASD), but the literature is limited and inconsistent. We tested the hypothesis that maternal exposure to stressful life events would be associated with increased risks of offspring ASD, and that these risks would be highest for exposures during the prenatal period. Methods and Results We used prospectively collected data from two large population based studies in Sweden and England. In the Swedish study of 4429 ASD cases and 43277 controls, our exposure comprised the occurrence of any severe life event before and during pregnancy and the child's early life. In the English study (maximum n = 11554, ASD n = 72), we studied the risk of offspring ASD in relation to a combined maternal exposure to multiple (up to 42) common and rare life events, as well as their perceived impact upon the mother during pregnancy and early life. In crude and adjusted regression analyses in both studies, we found no evidence of an association between prenatal life events, or their number and perceived impact and the risk of offspring ASD. Sub-group analysis of ASD with and without intellectual disability in the Swedish study yielded similar results. Conclusion We found no evidence to support the hypotheses that exposure to stressful life events during the prenatal period is associated with an increased risk of offspring ASD

Dental associations with blood mercury in pregnant women

OBJECTIVES: There is curiosity concerning the source of mercury that is absorbed into the mother's blood and which may affect the developing fetus. This study therefore sets out to determine the extent to which dental amalgam (DA) may contribute to total blood mercury (TBHg) levels of pregnant women in the UK. METHODS: Whole blood samples and information on diet and socio‐demographic factors were collected from pregnant women (n = 4484) enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). The whole blood samples were assayed for total mercury levels using inductively coupled plasma dynamic reaction cell mass spectrometry (ICP‐DRC‐MS), and the women were retrospectively asked about features of their dental care during the pregnancy. Linear regression was used to estimate the relative contributions of DA to TBHg levels (log‐transformed) based on R (2) values, compared to the results from dietary and socio‐demographic variables. RESULTS: The contribution to the variance of the mothers' TBHg levels by dental variables was 6.47%, a figure comparable to the 8.75% shown for seafood consumption in this population. Dietary and dental variables explained 20.16% of the variance, with socio‐demographic variables contributing only a further 3.40%. The number of amalgams in the mouth at the start of pregnancy accounted for most of the variance in dental variables. CONCLUSIONS: Dental amalgam contributes a comparable amount of variance in TBHg to seafood consumption in this population. However, because the measures of DA exposure were imprecise, these findings are likely to be an underestimate. There is no evidence to date in the literature that fetal exposures to mercury from maternal DAs have adverse effects on the developing child, but long‐term studies are warranted

Dependence of Deodorant Usage on ABCC11 Genotype:Scope for Personalized Genetics in Personal Hygiene

Earwax type and axillary odor are genetically determined by rs17822931, a single-nucleotide polymorphism (SNP) located in the ABCC11 gene. The literature has been concerned with the Mendelian trait of earwax, although axillary odor is also Mendelian. Ethnic diversity in rs17822931 exists, with higher frequency of allele A in east Asians. Influence on deodorant usage has not been investigated. In this work, we present a detailed analysis of the rs17822931 effect on deodorant usage in a large (N∼17,000 individuals) population cohort (the Avon Longitudinal Study of Parents and Children (ALSPAC)). We found strong evidence (P=3.7 × 10(−20)) indicating differential deodorant usage according to the rs17822931 genotype. AA homozygotes were almost 5-fold overrepresented in categories of never using deodorant or using it infrequently. However, 77.8% of white European genotypically nonodorous individuals still used deodorant, and 4.7% genotypically odorous individuals did not. We provide evidence of a behavioral effect associated with rs17822931. This effect has a biological basis that can result in a change in the family's environment if an aerosol deodorant is used. It also indicates potential cost saving to the nonodorous and scope for personalized genetics usage in personal hygiene choices, with consequent reduction of inappropriate chemical exposures for some

Measurement of the orientation of buffer-gas-cooled, electrostatically-guided ammonia molecules

AbstractThe extent to which the spatial orientation of internally and translationally cold ammonia molecules can be controlled as molecules pass out of a quadrupole guide and through different electric field regions is examined. Ammonia molecules are collisionally cooled in a buffer gas cell, and are subsequently guided by a three-bend electrostatic quadrupole into a detection chamber. The orientation of ammonia molecules is probed using (2+1) resonance-enhanced multiphoton ionisation (REMPI), with the laser polarisation axis aligned both parallel and perpendicular to the time-of-flight axis. Even with the presence of a near-zero field region, the ammonia REMPI spectra indicate some retention of orientation. Monte Carlo simulations propagating the time-dependent Schrödinger equation in a full basis set including the hyperfine interaction enable the orientation of ammonia molecules to be calculated – with respect to both the local field direction and a space-fixed axis – as the molecules pass through different electric field regions. The simulations indicate that the orientation of ∼95% of ammonia molecules in JK=11 could be achieved with the application of a small bias voltage (17V) to the mesh separating the quadrupole and detection regions. Following the recent combination of the buffer gas cell and quadrupole guide apparatus with a linear Paul ion trap, this result could enable one to examine the influence of molecular orientation on ion-molecule reaction dynamics and kinetics