%0 Journal Article
%T Novel pathogenic OCRL mutations and genotype-phenotype analysis of Chinese children affected by oculocerebrorenal syndrome: two cases and a literature review.
%A Zhang Y
%A Deng L
%A Chen X
%A Hu Y
%A Chen Y
%A Chen K
%A Zhou J
%J BMC Med Genomics
%V 14
%N 1
%D Sep 2021 6
%M 34488756
%F 3.622
%R 10.1186/s12920-021-01069-9
%X Oculocerebrorenal syndrome of Lowe is a rare X-linked disorder characterized by congenital cataracts, mental retardation, and proximal tubulopathy. This condition is caused by a mutation of OCRL gene (located at chromosome Xq26.1), which encodes an inositol polyphosphate 5-phosphatase.<BR>We identified two novel OCRL mutations in two unrelated Chinese boys, each with a severe phenotype of Lowe syndrome. A novel de novo deletion (hemizygous c.659_662delAGGG, p.E220Vfs*29) was present in patient 1 and a novel splicing mutation (hemizygous c.2257-2A > T) that was maternally inherited was present in patient 2. A renal biopsy in patient 2 indicated mild mesangial proliferative glomerulonephritis, mild focal mononuclear cells infiltration, and interstitial focal fibrosis. Moreover, renal expression of OCRL-1 protein in patient 2 was significantly reduced compared to a control patient with thin basement membrane disease.<BR>This study reports two novel OCRL variants associated with severe ocular and neurologic deficiency, despite only mild renal dysfunction. Based on our two patients and a literature review, the genotype-phenotype correlation of OCRL mutations with this severe phenotype of Lowe syndrome suggest a possible clustering of missense, deletion, and nonsense mutations in the 5-phosphatase domain and Rho-GAP domain in the Chinese population.