title: LRP5-linked osteoporosis-pseudoglioma syndrome mimicking isolated microphthalmia.
abstract: Microphthalmia is defined as the measurement of the total axial length of the eyeball to be below average of the two standard deviation according to the age. While several genes have been identified so far related to microphthalmia, the genetic etiology of the disease has not been fully understood because of genetic heterogeneity observed in this disease. After exclusion of the genes that had been known to be the cause of microphthalmia, we performed homozygosity mapping and exome sequencing to clarify the genetic etiology of the bilateral microphthalmia in this family. When the results of the exome and microarray data were considered together as a splice-site mutation in LRP5 gene [c.2827 + 1G > A], which is known to be important for eye development and Wnt receptor signaling pathway, was found to be the cause of microphthalmia in our family. It was understood that after finding this mutation, when bone mineral density was measured with DXA in the family whose ages range between 19 and 28 and who have no bone problem before, osteoporosis was diagnosed. It was also understood that microphthalmia found in this family is a clinical finding of OPPG syndrome.
authors.affiliation: Department of Biological Sciences, Middle East Technical University (METU), Ankara, Turkey; Gazi University Faculty of Medicine, Department of Medical Genetics, Besevler, Ankara, Turkey.
authors.forename: Sezen Guntekin
authors.initials: SG
authors.lastname: Ergun
authors.affiliation: Brain Research Centre, Ankara University, Mamak, Ankara, Turkey.
authors.forename: Guvem Gumus
authors.initials: GG
authors.lastname: Akay
authors.affiliation: Gazi University Faculty of Medicine, Department of Medical Genetics, Besevler, Ankara, Turkey.
authors.forename: Mehmet Ali
authors.initials: MA
authors.lastname: Ergun
authors.affiliation: Gazi University Faculty of Medicine, Department of Medical Genetics, Besevler, Ankara, Turkey. Electronic address: ferdaep@yahoo.com.
authors.forename: E Ferda
authors.initials: EF
authors.lastname: Perçin
mesh_terms: D000328:Adult; D001483:Base Sequence; D015519:Bone Density / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics*; D008297:Male; D008850:Microphthalmos / Q000175:diagnosis / Q000235:genetics*; D010013:Osteogenesis Imperfecta / Q000175:diagnosis / Q000235:genetics*; D010024:Osteoporosis / Q000175:diagnosis / Q000235:genetics*; D060490:Receptors, Wnt / Q000235:genetics; D017422:Sequence Analysis, DNA; D060449:Wnt Signaling Pathway / Q000502:physiology; D055815:Young Adult
chemical_list: C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060490:Receptors, Wnt
keywords: Exome sequencing; Homozygosity mapping; LRP5; Microphthalmia; OPPG