Atypical phenotypes and novel OCRL variations in Southern Chinese patients with Lowe syndrome

Abstract

Abstract Background: Lowe syndrome is an uncommon genetic disorder that follows an X-linked recessive inheritance pattern. It is defined by the occurrence of congenital cataracts, psychomotor retardation, and dysfunctional proximal renal tubules. This study examined the clinical and genetic features of eight children diagnosed with Lowe syndrome in Southern China. Methods: Whole-exome sequencing was performed on eight Lowe syndrome patients from three medical institutes in Southern China, and clinical and genetic data were collected and analyzed retrospectively. Results: In our cohort, the clinical symptoms of the eight Lowe syndrome individuals varied. One patient was diagnosed with Lowe syndrome but did not have congenital cataracts. All patients had psychomotor retardation, short stature, low molecular weight proteinuria, and albuminuria. The clinical characteristics also included elevated creatine kinase (CK)/ aspartate aminotransferase (AST)/ lactate dehydrogenase (LDH) (87.5%), cryptorchidism (66.7%), renal rickets (37.5%), renal tubular acidosis (37.5%), phosphaturia (37.5%), hypercalciuria (37.5%), nephrocalcinosis (25%) and glycosuria (25%). Eight variations in OCRLwere identified in all eight patients with Lowe syndrome, involving three known and five novel variations. All variations are located in exons 8-23 and occur in functional domains. Three novel nonsense variations were classified as pathogenic. Two patients with novel missense variations classified as uncertain significance showed typical severe phenotypes. Conclusion: This study describes the first case of an atypical Lowe syndrome patient without congenital cataracts in China and identifies novel OCRL gene variants, which broadens the genetic and symptomatic range for Lowe syndrome.