부산대학교 도서관

BackgroundLowe syndrome (LS) is an X linked disease caused by pathogenic variants in the OCRLgene that impacts approximately 1 in 500 000 children. Classic features include congenital cataract, cognitive/behavioural impairment and renal tubulopathy.MethodsThis study is a retrospective review of clinical features reported by family based survey conducted by Lowe Syndrome Association. Frequency of non-ocular clinical feature(s) of LS and their age of onset was summarised. An LS-specific therapy effectiveness scale was used to assess the response to the administered treatment. Expression of OCRLand relevant neuropeptides was measured in postmortem human brain by qPCR. Gene expression in the mouse brain was determined by reanalysis of publicly available bulk and single cell RNA sequencing.ResultsA total of 137 individuals (1 female, 89.1% white, median age 14 years (range 0.8–56)) were included in the study. Short stature (height <3rd percentile) was noted in 81% (n=111) individuals, and 15% (n=20) received growth hormone therapy. Undescended testis was reported in 47% (n=64), and median age of onset of puberty was 15 years. Additional features were dental problems (n=77, 56%), bone fractures (n=63, 46%), hypophosphataemia (n=60, 44%), developmental delay and behavioural issues. OCRLis expressed in human and mouse hypothalami, and in hypothalamic cell clusters expressing Ghrh, Sst, Oxt, Pomcand pituitary cells expressing Ghand Prl.ConclusionsThere is a wide spectrum of the clinical phenotype of LS. Some of the features may be partly driven by the loss of function of OCRLin the hypothalamus and the pituitary.