Biallelic variants in CRIPT cause a Rothmund-Thomson-like syndrome with increased cellular senescence.

PURPOSE: Rothmund-Thomson syndrome (RTS) is characterized by poikiloderma, sparse hair, small stature, skeletal defects, cancer, and cataracts, resembling features of premature aging. RECQL4 and ANAPC1 are the 2 known disease genes associated with RTS in >70% of cases. We describe RTS-like features in 5 individuals with biallelic variants in CRIPT (OMIM 615789). METHODS: Two newly identified and 4 published individuals with CRIPT variants were systematically compared with those with RTS using clinical data, computational analysis of photographs, histologic analysis of skin, and cellular studies on fibroblasts. RESULTS: All CRIPT individuals fulfilled the diagnostic criteria for RTS and additionally had neurodevelopmental delay and seizures. Using computational gestalt analysis, CRIPT individuals showed greatest facial similarity with individuals with RTS. Skin biopsies revealed a high expression of senescence markers (p53/p16/p21) and the senescence-associated ß-galactosidase activity was elevated in CRIPT-deficient fibroblasts. RECQL4- and CRIPT-deficient fibroblasts showed an unremarkable mitotic progression and unremarkable number of mitotic errors and no or only mild sensitivity to genotoxic stress by ionizing radiation, mitomycin C, hydroxyurea, etoposide, and potassium bromate. CONCLUSION: CRIPT causes an RTS-like syndrome associated with neurodevelopmental delay and epilepsy. At the cellular level, RECQL4- and CRIPT-deficient cells display increased senescence, suggesting shared molecular mechanisms leading to the clinical phenotypes.

Knowledge and Attitude Toward Child Safety Seat Use in Saudi Arabia: A Cross-Sectional Study.

Background Car safety seats (CSS) are a well-established strategy to reduce injuries and fatalities among children involved in road traffic accidents. However, the use of CSS is generally low globally due to limited knowledge of its benefits. This study assessed parents' knowledge and attitudes toward CSS in Saudi Arabia. Methods This cross-sectional study used an online self-administered survey distributed among residents in different regions of Saudi Arabia to assess their knowledge and attitude toward CSS. Data were analyzed using the statistical package for the social sciences (SPSS) version 23.0 (IBM Corp., Armonk, NY). Results A total of 383 Saudi residents participated in the study. The mean age was 37.14 ±9.10 years, with a female predominance (62.1%, n=238). One-third of the participants were from the western region of Saudi Arabia (30.3%, n=109). Non-use of CSS was reported by 25.8% of the participants, while 11.7% reported that they rarely used CSS. The mean total knowledge score was 2.15 (range 0 -3). A lower knowledge score was significantly associated with a lower educational level (p=0.008), not having information regarding CSS (p=0.005), none or rare use of CSS by the parent (p<0.001), and the use of media or self-education as a source of information regarding CSS (p=0.002). The mean attitude score was 12.52 (range 4 -20). The attitude score was significantly associated with gender (p=0.002), education (p=0.014), number of children (p=0.005), monthly family income (p=0.028), use of CSS by people other than the parent (p<0.001), information about CSS use in the car (p<0.002), source of information (p<0.001), and use of CSS by the parent (p<0.001). Conclusions The knowledge and attitude of the Suadi population toward CSS use are inadequate, highlighting the need to enhance awareness and understanding of the importance of CSS use.