Non-ubiquitous expression of core spliceosomal protein SmB/B' in chick and mouse embryos.

BACKGROUND: Although splicing is an integral part of the expression of many genes in our body, genetic syndromes with spliceosomal defects affect only specific tissues. To help understand the mechanism, we investigated the expression pattern of a core protein of the major spliceosome, SmB/B' (Small Nuclear Ribonucleoprotein Polypeptides B/B'), which is encoded by SNRPB. Loss-of-function mutations of SNRPB in humans cause cerebro-costo-mandibular syndrome (CCMS) characterized by rib gaps, micrognathia, cleft palate, and scoliosis. Our expression analysis focused on the affected structures as well as non-affected tissues, using chick and mouse embryos as model animals. RESULTS: Embryos at young stages (gastrula) showed ubiquitous expression of SmB/B'. However, the level and pattern of expression became tissue-specific as differentiation proceeded. The regions relating to CCMS phenotypes such as cartilages of ribs and vertebrae and palatal mesenchyme express SmB/B' in the nucleus sporadically. However, cartilages that are not affected in CCMS also showed similar expressions. Another spliceosomal gene, SNRNP200, which mutations cause retinitis pigmentosa, was also prominently expressed in cartilages in addition to the retina. CONCLUSION: The expression of SmB/B' is spatiotemporally regulated during embryogenesis despite the ubiquitous requirement of the spliceosome, however, the expression pattern is not strictly correlated with the phenotype presentation.

Facial photoprotection in xeroderma pigmentosum (XP) patients: Validation of a new self-reported questionnaire of adherence.

BACKGROUND/PURPOSE: Adherence to photoprotection is the only way to prevent skin cancers and eye disease in xeroderma pigmentosum (XP). No validated self-report questionnaire exists for assessing adherence to photoprotection practices in individuals with XP. We sought to validate a self-reported measure of adherence to face photoprotection in this population. METHODS: Sixty six XP patients recruited from the patient list of the XP specialist service in London, UK, completed a questionnaire of adherence to specific photoprotection behaviours. We measured objective ultraviolet radiation (UVR) exposure to the face continuously for 21 days with a wristworn UVR electronic dosimeter combined with a daily photoprotection diary. Reliability and convergent validity of the questionnaire were tested in relation to overall UVR exposure, UVR dose to the face, daily photoprotection activities, other self-reported photoprotection practices and clinical ratings of patient's protection. RESULTS: Internal consistency of the questionnaire was satisfactory. Questionnaire total scores were concordant with objective UVR exposure and UVR dose to the face. However, not all participants who reported good/excellent face photoprotection on the questionnaire recorded high levels of photoprotection in the daily diary. Correlations between the questionnaire and other practices and the clinical rating ranged from small to large in size. There was no correlation between the level of face photoprotection and self-reported avoidance of going outside. CONCLUSIONS: Our questionnaire was reliable and had good convergent validity with other indicators of photoprotection. This questionnaire could assist clinicians to detect low levels of adherence, and the methodology used to develop validated questionnaires for other photosensitive conditions.

Psychological correlates of adherence to photoprotection in a rare disease: International survey of people with Xeroderma Pigmentosum.

OBJECTIVES: Xeroderma pigmentosum (XP) is an extremely rare genetic disorder (approximately 100 known cases in the United Kingdom), where DNA damage caused by ultraviolet radiation in daylight cannot be repaired. Adherence to photoprotection is essential to prevent skin cancer. We investigated psychological correlates of photoprotection in the XP population of Western Europe and the United States. DESIGN: Cross-sectional survey of adults with XP and caregivers of patients <16 years and those with cognitive impairment in the United Kingdom, Germany, the United States, and France (n = 156). METHODS: Photoprotection activities to protect the face and body when outdoors; avoidance of going outside during daylight hours; intention; self-efficacy; and social support were assessed using measures developed for this study. Participants answered questions about their illness representations of XP (BIPQ); beliefs about photoprotection (BMQ); automaticity (i.e., without conscious effort) (SRBAI); clinical and demographic characteristics. Ordinal logistic regressions determined factors associated with photoprotection. RESULTS: One third did not achieve optimal face photoprotection. After controlling for demographic and clinical factors, modifiable correlates of higher photoprotection included greater perceived control of XP, stronger beliefs in necessity and effectiveness of photoprotection, and higher intention. Avoidance of going outside was associated with greater photoprotection concerns, more serious illness consequences, and higher XP-related distress. Greater automaticity and higher self-efficacy were associated with better protection across all outcomes. CONCLUSIONS: Approximately half of all known cases across three European countries participated. Identified modifiable predictors of photoprotection may be targeted by interventions to reduce the incidence of skin cancers in the immediate future, when a treatment breakthrough is unlikely. Statement of contribution What is already known on this subject? Adherence to photoprotection in other populations at elevated risk from skin cancer is poor; however, the level in XP is unknown. Research across chronic conditions shows that adherence to treatment and lifestyle recommendations are influenced by illness perceptions, self-efficacy, and treatment beliefs. Studies on photoprotection conducted with the general population have found that perceived risk, perceptions of ultraviolet radiation (UVR) protection, self-efficacy for the behaviour, and automaticity (behaviours that are enacted with little conscious awareness) are related to better photoprotection. What does this study add? This is the first international survey to examine adherence and its correlates in people with XP (an under-researched group at very high risk of fatal skin cancer). Adherence varies and at least one third have potential for improvement. Perceptions about XP, photoprotection beliefs, self-efficacy, intention, and automaticity were associated with photoprotection of the face and body when outdoors. Negative emotional representations of XP were associated with avoidance of going outside during daylight hours.