Clinical and genetic analysis of an infant with Lowe syndrome caused by exonic duplication of OCRL gene / 中华医学遗传学杂志

Objective@#To explore the genetic basis of an infant featuring congenital cataract, developmental delay and proteinuria.@*Methods@#Clinical data and peripheral blood samples of the family were collected. Potential variants were screened by using targeted capture and high-throughput sequencing on a NextSeq 500 platform. Suspected variant was verified by quantitative PCR. Pathogenicity of the candidate variant was predicted based on clinical presentation and laboratory tests.@*Results@#The infant’s phenotypes included brain development retardation and proteinuria. Cranial MRI indicated widening of cerebral fissure, bilateral frontal and temporal subarachnoid cavities, and dysplasia of white matter myelination in posterior angular of ventricle. A novel duplication of exons 5 to 16 of the OCRL gene was found in the patient. His mother has carried the same duplication variant.@*Conclusion@#The duplication variant of the OCRL gene probably underlies the oculo-cerebro-renal syndrome in the infant. Due to the heterogeneity of its clinical manifestation, pertinent genetic detection is essential for acurrate diagnosis of patients who have the related phenotypes.

Clinical features and OCRL mutation analysis in a case of infant Lowe syndrome / 中国病理生理杂志

[ ABSTRACT ] AIM: To characterize the phenotypic and genetic features of a patient with Lowe syndrome. METHODS:The clinical data and the MRI of a ten-month-old patient were analyzed.At the same time, all exons of the OCRL gene of the patient and his parents were amplified and Sanger-sequenced.RESULTS:Clinical analysis revealed that the patient has abnormal vision, nystagmus, congenital cataract, hypotonia, proteinuria, hematuria and psychomotor retar-dation.MRI showed white matter myelination delay, bilateral frontal and temporal dysplasia, and subarachnoid cavity en-largement.The results of PCR and Sanger sequencing detected a de novo mutation, NM_000276.3: c.1280-1281delTT (p.Cys428Hisfs*2), a deletion causing a frame shift.To our knowledge, this mutation in OCRL gene has not been repor-ted previously.CONCLUSION:The clinical manifestations suggested a phenotype of Lowe syndrome, and molecular ge-netic testing confirmed the diagnosis.The novel de novo mutation enriches the OCRL mutation spectrum.

Lowe syndrome with novel OCRL mutations in Chinese children:report of two cases / 临床儿科杂志

Objective To study the clinical and genetic features of Lowe syndrome. Methods The clinical data and test results of OCRL gene from two children with Lowe syndrome were analyzed. The related literatures were reviewed. Re-sults Two male patients all presented with low molecular proteinuria, hypercalciuria, rickets and nephrolithiasis. Patient 2 had renal tubular acidosis, glycosuria and cryptochism. Patient 1 was found to have abnormal vision and congenital cataract soon after birth and treated surgically. Patient 1 also had psychomotor retardation and the cranial magnetic resonance ima-ging (MRI) showed agenesis of the corpus callosum. Patient 2 did not have obviously extra-renal symptoms, but was found to have mild cataract by a meticulous ophthalmological examination. MRI showed cerebral hypoplasia and myelination delay and mental retardation was gradually appeared during follow-up. Two OCRL gene mutations were detected. A splice site mutation NG_008638.1:g.46846-46848delTAA/insC was found in patient 1 and a frame shift mutation NM_000276.3:c.321delC in exon 5 was found in patient 2. Both mutations were not reported previously. Conclusions The diagnosis of Lowe syndrome is mainly by clinical manifestations and test of OCRL gene. Lowe syndrome needs to be included in the differential diagnosis of a patient with congenital cataract and renal tubulopathy. Two novel mutations in the OCRL gene were identiifed.