AbstractBackgroundLowe syndrome is a rare X‑linked syndrome that is characterized by involvement of the eyes, central nervous system, and kidneys. The aim of the present study was to determine the molecular basis of four patients with congenital cataract, infantile congenital hypotonia, and proximal renal tubular defect.MethodsFour children who met the clinical manifestations of Lowe syndrome were enrolled in this study. Patients’ clinical information on eyes, central nervous system, kidneys, and family histories, etc., were reviewed and analyzed. After obtaining informed consent, we performed a mutation analysis of OCRL gene using direct sequencing. Because of failure of PCR amplification, low coverage shortread whole genome sequencing (CNVseq) analysis was performed on one proband. Real‐time PCR was subsequently performed to confirm the CNV that was detected from the CNVseq results.ResultsWe identified three OCRL allelic variants, including two novel missense mutations (c.1423C>T/p.Pro475Ser, c.1502T>G/p.Ile501Ser) and one recurrent nonsense mutation (c.2464C>T/p.Arg822Ter). Various bioinformatic tools revealed scores associated with potential pathogenic effects for the two missense variants, and protein alignments revealed that both variants affected an amino acid highly conserved among species. Since deletion of the entire gene was suspected in a patient, CNVseq was used, identifying an interstitial deletion to approximately 190 kb, encompassing OCRL, and SMARCA1 gene. Moreover, the hemizygous CNV was confirmed by qPCR. Reviewing another case reported in the literature, we found that the deletion of OCRL and nearby genes may contribute to a more severe phenotype and premature death.ConclusionsThis is the first report of an interstitial deletion encompassing OCRL and SMARCA1 gene in Lowe syndrome. Our results expand the spectrum of mutations of the OCRL gene in Chinese population. Moreover, whole‐genome sequencing presents a comprehensive and reliable approach for detecting genomic copy number variation in patients or carriers in the family with rare inherited disorders.