Retinitis pigmentosa (RP) comprises a clinically and genetically heterogeneous group of diseases that afflicts approximately 1.5 million people worldwide. Affected individuals suffer from a progressive degeneration of the photoreceptors, eventually resulting in severe visual impairment. To isolate candidate genes for chorioretinal diseases, we cloned cDNAs specifically or preferentially expressed in the human retina and the retinal pigment epithelium (RPE) through a novel suppression subtractive hybridization (SSH) method. One of these cDNAs (RET3C11) mapped to chromosome 1q31-q32.1, a region harbouring a gene involved in a severe form of autosomal recessive RP characterized by a typical preservation of the para-arteriolar RPE (RP12; ref. 3). The full-length cDNA encodes an extracellular protein with 19 EGF-like domains, 3 laminin A G-like domains and a C-type lectin domain. This protein is homologous to the Drosophila melanogaster protein crumbs (CRB), and denoted CRB1 (crumbs homologue 1). In ten unrelated RP patients with preserved para-arteriolar RPE, we identified a homozygous AluY insertion disrupting the ORF, five homozygous missense mutations and four compound heterozygous mutations in CRB1. The similarity to CRB suggests a role for CRB1 in cell-cell interaction and possibly in the maintenance of cell polarity in the retina. The distinct RPE abnormalities observed in RP12 patients suggest that CRB1 mutations trigger a novel mechanism of photoreceptor degeneration.

Leber congenital amaurosis (LCA, MIM 204000) accounts for at least 5% of all inherited retinal disease and is the most severe inherited retinopathy with the earliest age of onset. Individuals affected with LCA are diagnosed at birth or in the first few months of life with severely impaired vision or blindness, nystagmus and an abnormal or flat electroretinogram (ERG). Mutations in GUCY2D (ref. 3), RPE65 (ref. 4) and CRX (ref. 5) are known to cause LCA, but one study identified disease-causing GUCY2D mutations in only 8 of 15 families whose LCA locus maps to 17p13.1 (ref. 3), suggesting another LCA locus might be located on 17p13.1. Confirming this prediction, the LCA in one Pakistani family mapped to 17p13.1, between D17S849 and D17S960-a region that excludes GUCY2D. The LCA in this family has been designated LCA4 (ref. 6). We describe here a new photoreceptor/pineal-expressed gene, AIPL1 (encoding aryl-hydrocarbon interacting protein-like 1), that maps within the LCA4 candidate region and whose protein contains three tetratricopeptide (TPR) motifs, consistent with nuclear transport or chaperone activity. A homozygous nonsense mutation at codon 278 is present in all affected members of the original LCA4 family. AIPL1 mutations may cause approximately 20% of recessive LCA, as disease-causing mutations were identified in 3 of 14 LCA families not tested previously for linkage.

Aims:The role of arts and music in supporting subjective wellbeing (SWB) is increasingly recognised. Robust evidence is needed to support policy and practice. This article reports on the first of four reviews of Culture, Sport and Wellbeing (CSW) commissioned by the Economic and Social Research Council (ESRC)-funded What Works Centre for Wellbeing (https://whatworkswellbeing.org/).Objective:To identify SWB outcomes for music and singing in adults.Methods:Comprehensive literature searches were conducted in PsychInfo, Medline, ERIC, Arts and Humanities, Social Science and Science Citation Indexes, Scopus, PILOTS and CINAHL databases. From 5,397 records identified, 61 relevant records were assessed using GRADE and CERQual schema.Results:A wide range of wellbeing measures was used, with no consistency in how SWB was measured across the studies. A wide range of activities was reported, most commonly music listening and regular group singing. Music has been associated with reduced anxiety in young adults, enhanced mood and purpose in adults and mental wellbeing, quality of life, self-awareness and coping in people with diagnosed health conditions. Music and singing have been shown to be effective in enhancing morale and reducing risk of depression in older people. Few studies address SWB in people with dementia. While there are a few studies of music with marginalised communities, participants in community choirs tend to be female, white and relatively well educated. Research challenges include recruiting participants with baseline wellbeing scores that are low enough to record any significant or noteworthy change following a music or singing intervention.Conclusions:There is reliable evidence for positive effects of music and singing on wellbeing in adults. There remains a need for research with sub-groups who are at greater risk of lower levels of wellbeing, and on the processes by which wellbeing outcomes are, or are not, achieved.

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