Lowe综合征(LS)是由OCRL基因的致病变异引起的X连锁疾病,影响约500,000名儿童中的1名。经典特征包括先天性白内障,认知/行为障碍和肾小管病。
本研究是对Lowe综合征协会进行的基于家庭的调查报告的临床特征的回顾性回顾。总结了LS的非眼部临床特征的频率及其发病年龄。使用LS特异性治疗有效性量表来评估对施用的治疗的反应。通过qPCR测量死后人脑中OCRL和相关神经肽的表达。小鼠脑中的基因表达通过公开可用的批量和单细胞RNA测序的再分析来确定。
共有137个人(1名女性,89.1%白色,中位年龄14岁(范围0.8~56岁)纳入研究.在81%(n=111)的个体中注意到身材矮小(身高<第三百分位数),15%(n=20)接受生长激素治疗。据报道,有47%的睾丸未降(n=64),青春期发病年龄中位数为15岁.其他特征是牙齿问题(n=77,56%),骨折(n=63,46%),低磷酸盐血症(n=60,44%),发育迟缓和行为问题。OCRL在人和小鼠下丘脑中表达,在表达Ghrh的下丘脑细胞簇中,Sst,Oxt,Pomc和表达Gh和Prl的垂体细胞。
存在广泛的LS临床表型。某些特征可能部分是由下丘脑和垂体中OCRL功能的丧失引起的。
Lowe syndrome (LS) is an X linked disease caused by pathogenic variants in the OCRL gene that impacts approximately 1 in 500 000 children. Classic features include congenital cataract, cognitive/behavioural impairment and renal tubulopathy.
This 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 OCRL and 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.
A 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. OCRL is expressed in human and mouse hypothalami, and in hypothalamic cell clusters expressing Ghrh, Sst, Oxt, Pomc and pituitary cells expressing Gh and Prl.
There is a wide spectrum of the clinical phenotype of LS. Some of the features may be partly driven by the loss of function of OCRL in the hypothalamus and the pituitary.