RESUMEN
In genetic disease, an accurate expression landscape of disease genes and faithful animal models will enable precise genetic diagnoses and therapeutic discoveries, respectively. We previously discovered that variants in NOS1AP , encoding nitric oxide synthase 1 (NOS1) adaptor protein, cause monogenic nephrotic syndrome (NS). Here, we determined that an intergenic splice product of N OS1AP / Nos1ap and neighboring C1orf226/Gm7694 , which precludes NOS1 binding, is the predominant isoform in mammalian kidney transcriptional and proteomic data. Gm7694 -/- mice, whose allele exclusively disrupts the intergenic product, developed NS phenotypes. In two human NS subjects, we identified causative NOS1AP splice variants, including one predicted to abrogate intergenic splicing but initially misclassified as benign based on the canonical transcript. Finally, by modifying genetic background, we generated a faithful mouse model of NOS1AP -associated NS, which responded to anti-proteinuric treatment. This study highlights the importance of intergenic splicing and a potential treatment avenue in a mendelian disorder.
RESUMEN
AIMS AND OBJECTIVES: To explore the experiences of community nurses and home carers, in caring for patients on home enteral nutrition. BACKGROUND: The number of patients on home enteral nutrition is on the increase due to advancement in technology and shift in focus of providing care from acute to community care settings. METHODS: A mixed-method approach was adopted. (i) A face-to-face survey design was used to elicit experience of carers of patients on home enteral nutrition. (ii) Focus group interviews were conducted with community nurses. RESULTS: Ninety-nine carers (n = 99) were recruited. Patient's mean age that they cared for was aged 77.7 years (SD = 11.2), and they had been on enteral feeding for a mean of 29 months (SD = 23.0). Most were bed-bound (90%) and required full assistance with their feeding (99%). Most were not on follow-up with dietitians (91%) and dentists (96%). The three most common reported gastrointestinal complications were constipation (31%), abdominal distension (28%) and vomiting (22%). Twenty community nurses (n = 20) were recruited for the focus group interviews. Four main themes emerged from the analysis: (i) challenge of accessing allied health services in the community; (ii) shorter length of stay in the acute care setting led to challenges in carers' learning and adaptation; (iii) transition gaps between hospital and home care services; and (iv) managing expectations of family. CONCLUSION: To facilitate a better transition of care for patients, adequate training for carers, standardising clinical practice in managing patients with home enteral nutrition and improving communication between home care services and the acute care hospitals are needed. RELEVANCE TO CLINICAL PRACTICE: This study highlighted the challenges faced by community home care nurses and carers. Results of this study would help to inform future policies and practice changes that would improve the quality of care received by patients on home enteral nutrition.
