POT1 and multiple primary melanomas: the dermatological phenotype.

POT1 is the second most frequently reported gene (after CDKN2A) in familial melanoma. Pathogenic variants are associated with earlier onset and/or multiple primary melanomas (MPMs). To date, POT1 phenotypical reports have been largely restricted to associated malignancies, and description of the dermatological landscape has been limited. We identified 10 variants in n=18 of 384 (4.7%) unrelated individuals (n=13 MPMs; n=5 single primary melanomas) of European ancestry. Five variants were rare (minor allele frequency <0.001) or novel (two loss-of-function (LOF), one splice acceptor and two missense) and were predicted to be functionally significant, in five unrelated probands with MPMs (≥3 melanomas). We performed three-dimensional total body photography on both individuals with confirmed pathogenic LOF variants to characterise the dermatological phenotype. Total body naevus counts (≥2 mm diameter) were significantly higher (p=7.72×10-12) in carriers compared with a control population. Majority of naevi were on the probands' back and lower limb regions, where only mild to moderate ultraviolet (UV) damage was observed. Conversely, the head/neck region, where both probands exhibited severe UV damage, had comparably fewer naevi. We hypothesise that carriage of functionally significant POT1 variants is associated with increased naevus counts generally, and naevi >5 mm in diameter specifically and the location of these are independent of UV damage.

MITF E318K: A rare homozygous case with multiple primary melanoma.

MITF E318K moderates melanoma risk. Only five MITF E318K homozygous cases have been reported to date, one in association with melanoma. This novel report uses 3D total-body-photography (TBP) to describe the dermatological phenotype of a homozygous MITF E318K individual. The case, a 32-year-old male, was diagnosed with his first of six primary melanomas at 26 years of age. Five melanomas were located on the back and one in the groin. Two were superficial spreading. Three arose from pre-existing naevi and one was a rare naevoid melanoma. 3D-TBP revealed a high naevus count (n = 162) with pigmentation varying from light to dark. Most naevi generally (n = 90), and large (>5 mm diameter) and clinically atypical naevi specifically were located on the back where sun damage was mild. In contrast, naevi count was low (n = 25 total) on the head/neck and lower limbs where sun damage was severe. Thus, melanoma location correlated with naevi density, rather than degree of sun damage. In addition to the MITF E318K homozygosity, there was heterozygosity for four other moderate-risk variants, which may contribute to melanoma risk. Further research is warranted to explore whether melanomas in E318K heterozygous and other homozygotes coincide with regions of high naevi density as opposed to sun damage. This could inform future melanoma screening/surveillance.

Mobile apps for dementia awareness, support, and prevention - review and evaluation.

PURPOSE: This review aimed to document the characteristics and appraise the quality of dementia applications (apps) to support persons living with dementia and their caregivers. MATERIALS AND METHODS: Systematic searches of the Australian-based Google Play Store, Apple App Store, and relevant websites sought apps with dementia or Alzheimer's information, support for caregivers and persons living with dementia, or prevention content. Apps were screened and subsequently appraised via the mobile application review system (MARS). RESULTS: The majority of the final 75 dementia apps were free to download, but were only available on a single platform. Persons involved in caregiving were the primary audience. App content focused on dementia information, practical caregiving, and communication tips. Language options in addition to English were limited and few apps offered ongoing support. MARS appraisal identified few apps with good "Overall Quality" scores. Apps that were more comprehensive trended towards higher MARS scores. CONCLUSIONS: A composite lack of standardised quality indicators and commercial drivers of the marketplace present significant barriers for consumers seeking meaningful dementia information and support. Persons living with dementia and their caregivers would significantly benefit from social and organisational services that assist with navigating the app marketplace.Implications for rehabilitationThere is significant opportunity for quality digital innovations, including apps, to support home-based, independent dementia care.A composite lack of standardised quality indicators and commercial drivers of the app marketplace present significant barriers for persons living with dementia and their caregivers who seek apps with dementia information and support.Social and organisational services can support the dementia community through assistance with navigating the app marketplace for quality dementia information and support.