Characterization of a germline mosaicism in families with Lowe syndrome, and identification of seven novel mutations in the OCRL1 gene.

The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by major abnormalities of eyes, nervous system, and kidneys.
Mutations in the OCRL1 gene have been associated with the disease.
OCRL1 encodes a phosphatidylinositol 4, 5-biphosphate (PtdIns [4, 5] P2) 5-phosphatase.
We have examined the OCRL1 gene in eight unrelated patients with OCRL and have found seven new mutations and one recurrent in-frame deletion.
Among the new mutations, two nonsense mutations (R317X and E558X) and three other frameshift mutations caused premature termination of the protein.
A missense mutation, R483G, was located in the highly conserved PtdIns (4, 5) P2 5-phosphatase domain.
Finally, one frameshift mutation, 2799delC, modifies the C-terminal part of OCRL1, with an extension of six amino acids.
Altogether, 70% of missense mutations are located in exon 15, and 52% of all mutations cluster in exons 11-15. We also identified two new microsatellite markers for the OCRL1 locus, and we detected a germline mosaicism in one family.
This observation has direct implications for genetic counseling of Lowe syndrome families.. 
