Muireann Ni Chroinin

First implication of STRA6 mutations in isolated anophthalmia, microphthalmia, and coloboma: A new dimension to the STRA6 phenotype†

Microphthalmia, anophthalmia, and coloboma (MAC) are structural congenital eye malformations that cause a significant proportion of childhood visual impairments. Several disease genes have been identified but do not account for all MAC cases, suggesting that additional risk loci exist. We used single nucleotide polymorphism (SNP) homozygosity mapping (HM) and targeted next‐generation sequencing to identify the causative mutation for autosomal recessive isolated colobomatous microanophthalmia (MCOPCB) in a consanguineous Irish Traveller family. We identified a double‐nucleotide polymorphism (g.1157G>A and g.1156G>A; p.G304K) in STRA6 that was homozygous in all of the MCOPCB patients. The STRA6 p.G304K mutation was subsequently detected in additional MCOPCB patients, including one individual with Matthew‐Wood syndrome (MWS; MCOPS9). STRA6 encodes a transmembrane receptor involved in vitamin A uptake, a process essential to eye development and growth. We have shown that the G304K mutant STRA6 protein is mislocalized and has severely reduced vitamin A uptake activity. Furthermore, we reproduced the MCOPCB phenotype in a zebrafish disease model by inhibiting retinoic acid (RA) synthesis, suggesting that diminished RA levels account for the eye malformations in STRA6 p.G304K patients. The current study demonstrates that STRA6 mutations can cause isolated eye malformations in addition to the congenital anomalies observed in MWS. 32:1417–1426, 2011. ©2011 Wiley Periodicals, Inc.

Health-Related Quality of Life in Adolescents and Adults With Cystic Fibrosis: Physical and Mental Health Predictors

BACKGROUND: People with cystic fibrosis face substantial physical, psychological, and social challenges as they move into adolescence and adulthood, which are likely to impact on their health-related quality of life. This study sought to examine the relative importance of physical and mental health variables associated with health-related quality of life in this group. METHODS: Adults and adolescents (N = 174; ≥14 y old) from across 11 adult or pediatric cystic fibrosis clinics in the Republic of Ireland, completed a background questionnaire that contained self-reported physical health variables, pulmonary function (ie, FEV1%) and body mass index. Questionnaire packs also contained the Hospital Anxiety and Depression Scale (HADS) and the Cystic Fibrosis Questionnaire-Revised, which has been specifically designed to assess health-related quality of life in patients with cystic fibrosis. RESULTS: HADS depression and/or anxiety scores were negatively associated with 11 of the 12 Cystic Fibrosis Questionnaire-Revised domain scores. FEV1% was positively associated with 8 domains when controlling for HADS anxiety but only 4 domains when controlling for HADS depression. HADS anxiety and depression scores demonstrated larger effect sizes and explained a greater proportion of the variance than pulmonary function in 8 of the 12 Cystic Fibrosis Questionnaire-Revised domain scores. CONCLUSIONS: Mental health variables, depression and anxiety, were strongly associated with health-related quality of life in subjects with cystic fibrosis and demonstrated greater effect sizes and explained a higher proportion of the variance overall than the physical health indicators, FEV1% and body mass index, which highlighted the importance of screening for, and treating, depression and anxiety symptoms.

Online versus paper-based screening for depression and anxiety in adults with cystic fibrosis in Ireland: a cross-sectional exploratory study

Objective To compare online and paper-based screening for depression and anxiety in adults with cystic fibrosis (CF). Design and setting Cross-sectional study in CF clinics in Ireland and through the Cystic Fibrosis Ireland online community. Participants 160 adult patients aged 18 or above were recruited. Of these, 147 were included in the analysis; 83 online and 64 paper-based. The remaining 13 were excluded because of incomplete data. Measures Depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Data on pulmonary function (forced expiratory volume in 1 s %) and body mass index were self-reported based on clinical assessments. Sociodemographic data were collected. Results Compared with the paper-based participants, the online participants were more likely to be female (61.7% vs 48.4%), older (mean 32.2 vs 28.2 years) and were more likely to be married (32.5% vs 15.6%), living with their spouse or partner (42.5% vs 22.6%) and working either full time (33.7% vs 15.9%) or part time (30.1%vs 17.5%). The prevalence rates of elevated anxiety and depression were not significantly different (P=0.71 and P=0.56). HADS anxiety and depression scores were not statistically different between online (P=0.83) and paper-based (P=0.92) participants based on Mann-Whitney U test. A significant negative correlation was found between depression and pulmonary function (r=−0.39, P=0.01) and anxiety and pulmonary function (r=−0.36, P=0.02). Based on Cronbach’s alpha, there were no statistically significant differences between the online and paper-based participants on the internal consistency of the HADS anxiety (P=0.073) and depression (P=0.378) scales. Conclusions Our findings suggest that online and paper-based screening for depression and anxiety in adult patients with CF yield comparable findings on prevalence rates and scores, associations with health and internal consistency of subscales. This study highlights that online screening offers an alternative method to paper-based screening. Further research with a larger sample and assessment of measurement equivalence between online and paper based screening is needed to confirm our results.