Novel Homozygous LRP5 Mutations in Mexican Patients with Osteoporosis-Pseudoglioma Syndrome.

Autor:	Astiazarán MC; 1 Research Unit, Genetics Department, Institute of Ophthalmology , 'Conde de Valenciana,' Mexico City, Mexico ., Cervantes-Sodi M; 2 Departamento Clínico de Genética Médica, Hospital de Pediatría , Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico ., Rebolledo-Enríquez E; 3 Institute of Ophthalmology , 'Conde de Valenciana,' Mexico City, Mexico ., Chacón-Camacho O; 1 Research Unit, Genetics Department, Institute of Ophthalmology , 'Conde de Valenciana,' Mexico City, Mexico ., Villegas V; 1 Research Unit, Genetics Department, Institute of Ophthalmology , 'Conde de Valenciana,' Mexico City, Mexico ., Zenteno JC; 1 Research Unit, Genetics Department, Institute of Ophthalmology , 'Conde de Valenciana,' Mexico City, Mexico .; 4 Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico , Mexico City, Mexico .
Jazyk:	angličtina
Zdroj:	Genetic testing and molecular biomarkers [Genet Test Mol Biomarkers] 2017 Dec; Vol. 21 (12), pp. 742-746. Date of Electronic Publication: 2017 Nov 13.
DOI:	10.1089/gtmb.2017.0118
Abstrakt:	Aims: Osteoporosis-pseudoglioma syndrome (OPPG) is an uncommon autosomal recessive disorder characterized by the rare association of early-onset osteoporosis and severe ocular abnormalities such as persistent fetal vasculature and microphthalmia. Biallelic mutations in the low-density lipoprotein receptor-related protein-5 gene (LRP5) have been associated with OPPG. We present clinical and genetic data from three Mexican OPPG patients, a pair of sibs, and a sporadic case. Materials and Methods: Three patients underwent clinical examination, including a complete ophthalmic evaluation. Based on the clinical diagnosis of OPPG, the entire coding sequence of LRP5 was polymerase chain reaction-amplified and directly Sanger-sequenced. Genetic testing was extended to the parents of the affected patients. Results: Phenotypic variability was observed in the familial case and molecular analysis identified a novel homozygous c.1145C>T, p.(Pro382Leu) variant in both sibs. As expected, their parents were heterozygous carriers. The sporadic patient exhibited a severe osseous phenotype, microphthalmia, and neurological symptoms. In this patient, homozygosity for the c.442C>T, p.(Gln148*) variant was demonstrated, whereas her parents were heterozygous carriers. The p.(Pro382Leu) pathogenic mutation has been previously reported only in a compound heterozygous state in OPPG patients. Conclusions: Two novel homozygous missense and nonsense variants were demonstrated in three OPPG cases from Mexico. Our results expand the spectrum of disease-causing LRP5 mutations. This is the first report of OPPG in our population and our findings may potentially add to a genotype-phenotype correlation.
Databáze:	MEDLINE
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