RT Journal Article
SR Electronic
T1 Endocrine and behavioural features of Lowe syndrome and their potential molecular mechanisms
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 1171
OP 1178
DO 10.1136/jmedgenet-2022-108490
VO 59
IS 12
A1 Cecilia Sena
A1 Grazia Iannello
A1 Alicja A Skowronski
A1 Katelyn Dannheim
A1 Leonard Cheung
A1 Pankaj B Agrawal
A1 Joel N Hirschhorn
A1 Phillip Zeitler
A1 Charles A LeDuc
A1 George Stratigopoulos
A1 Vidhu V Thaker
YR 2022
UL http://jmg.bmj.com/content/59/12/1171.abstract
AB Background 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.Methods 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.Results 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.Conclusions 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.Data may be obtained from a third party and are not publicly available. Data can be requested from the Lowe Syndrome Association.