Genetic Analysis of Oculocerebrorenal Syndrome of Lowe
Genetic Analysis of Oculocerebrorenal Syndrome of Lowe
This study will investigate the genetic basis of oculocerebrorenal syndrome of Lowe (OCRL)-a
 rare X-linked disorder (carried by females and passed to males). Patients with OCRL have
 abnormal development of the eye lens, developmental delay, muscle weakness and kidney
 dysfunction.

 The study will examine DNA and cell samples obtained and archived from patients with OCRL
 enrolled in a previous protocol (HG008A) between 1996 and 1999. It will identify mutations in
 the OCRL1 gene responsible for OCRL in affected males and try to correlate them with specific
 biochemical or cellular activities (e.g., enzyme activity, protein stability, cellular
 localization and trafficking). When test results are available, the information will be
 communicated to the patients, their parents (if the patient is a minor) and their physicians,
 and families will receive genetic counseling.
Oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked disorder characterized by
 congenital cataracts, mental retardation, and renal tubular dysfunction. Patients with known
 or suspected OCRL were enrolled under previous protocol 96-HG-0008 that expired in 1998 and
 was not renewed. We are continuing studies of DNA and cell samples obtained and archived
 under our previous protocol to identify mutations in the OCRL1 gene responsible for Lowe
 syndrome and related disorders in affected males and attempt to correlate these mutations to
 particular biochemical or cellular phenotypes (enzyme activity, protein stability, cellular
 localization and trafficking). Information about genotypes will not be communicated back to
 the patients, their parents (if patient is a minor) or their physicians as part of this
 study.

 We are also continuing our investigations of heterogeneity in OCRL by studying collected cell
 cultures from our collaborator Dr. Steven Scheinman at Suny New York Medical University,
 Syracuse, from a group of patients with mutations in OCRL1 who have Dent disease,
 characterized by renal tubular dysfunction. These data, and the variability in the renal and
 CNS abnormalities that occur in OCRL are evidence for the existence of modifiers. We propose
 to identify genes that are differentially expressed in cells from OCRL patients, patients
 with Dent disease and OCRL1 mutations by gene expression analysis of RNA from patient
 samples.

 As part of our study on phenotypic and genetic heterogeneity in OCRL, mutation analysis
 resulted in the identification of mutations mostly in the second two-thirds of OCRL1.
 However, the OCRL1 mutations in the Dent disease patients have been found in the first third
 of OCRL1. We plan to send samples from Lowe syndrome patients without identified OCRL1
 mutations to a Dr. Steven Scheinman who will look for such OCRL1 mutations. He will be sent
 only coded samples and will look for such OCRL1 mutations. He will be sent only coded samples
 and will not have access to patient identifiers. This information will be used for research
 purposes only.
-  INCLUSION CRITERIA:

 Male gender, history of congenital cataracts, proximal renal tubular dysfunction, and
 developmental delay.