title: Characterization of a germline mosaicism in families with Lowe syndrome, and identification of seven novel mutations in the OCRL1 gene.
abstract: 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.
authors.affiliation: Laboratoire de Biochimie de l'ADN, CHU Grenoble, 4 Laboratoire BECP- EA 2019 UJF, DBMS, CEA, Grenoble, France.
authors.forename: V
authors.initials: V
authors.lastname: Satre
authors.forename: N
authors.initials: N
authors.lastname: Monnier
authors.forename: F
authors.initials: F
authors.lastname: Berthoin
authors.forename: C
authors.initials: C
authors.lastname: Ayuso
authors.forename: A
authors.initials: A
authors.lastname: Joannard
authors.forename: P S
authors.initials: PS
authors.lastname: Jouk
authors.forename: I
authors.initials: I
authors.lastname: Lopez-Pajares
authors.forename: A
authors.initials: A
authors.lastname: Megabarne
authors.forename: H J
authors.initials: HJ
authors.lastname: Philippe
authors.forename: H
authors.initials: H
authors.lastname: Plauchu
authors.forename: M L
authors.initials: ML
authors.lastname: Torres
authors.forename: J
authors.initials: J
authors.lastname: Lunardi
mesh_terms: D000595:Amino Acid Sequence; D005260:Female; D005820:Genetic Testing; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009030:Mosaicism; D009154:Mutation; D009800:Oculocerebrorenal Syndrome / Q000235:genetics*; D010375:Pedigree; D010744:Phosphoric Monoester Hydrolases; D011506:Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D011506:Proteins; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human