Analysis of LRP5 gene variants in a Chinese pedigree affected with Osteoporosis-pseudoglioma syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree with two individuals suffering from congenital blindness.@*METHODS@#Clinical data and peripheral blood samples of the pedigree were collected. Whole exome sequencing was carried out. Suspected variants were verified by Sanger sequencing. Pathogenicity of candidate variants was validated through searching of PubMed and related databases, and analyzed with bioinformatics software.@*RESULTS@#Both patients had congenital blindness and a history of multiple fractures. Other features have included microphthalmia and cornea opacity. One patient had normal intelligence, whilst the other had a language deficit. Both patients were found to harbor compound heterozygous variants of the LRP5 gene, namely c.1007_1015delGTAAGGCAG (p.C336X), c.4400G>A (p.R1467Q) and c.4600C>T (p.R1534X). The first one was derived from their mother, whilst the latter two were derived from their father. None of the three variants was detected in their elder sister.@*CONCLUSION@#The compound heterozygous variants of c.1007_1015delGTAAGGCAG (p.C336X) and c.4600C>T (p.R1534X) of the LRP5 gene probably underlay the pathogenesis of the Osteoporosis-pseudoglioma syndrome in this pedigree. The clinical significance of the c.4400G>A (p.R1467Q) variant has remained uncertain. Above finding has enriched the mutational spectrum of Osteoporosis-pseudoglioma syndrome.

The low-density lipoprotein receptor-related protein 5 (LRP5) 4037C>T polymorphism: candidate for susceptibility to type 1 diabetes mellitus

ABSTRACT Objective: The present study has investigated the association between low-density lipoprotein receptor-related protein 5 (LRP5) 4037C>T polymorphism and type 1 diabetes mellitus (T1DM) susceptibility in a Brazilian population. Subjects and methods: A total number of 134 T1DM patients and 180 normoglycemic individuals (NG) aged 6-20 years were studied. Glycated hemoglobin and glucose levels were determined. Genotyping of LRP5 4037C>T (rs3736228) was performed. Results: T1DM patients showed poor glycemic control. Genotypes in the codominant (CT: OR = 2.99 [CI 95%: 1.71-5.24], p < 0.001; TT: OR = 5.34 [CI 95%: 1.05-2702], p < 0.001), dominant (CT + TT: OR = 3.16 [CI 95%: 1.84-5.43], p < 0.001) and log-additive (OR = 2.78 [CI 95%: 1.70-4.52], p < 0.001) models, and LRP5 4037T allele (OR = 2.88, [CI 95%: 1.78-4.77], p < 0.001) were associated with an increased risk of developing T1DM. LRP5 4037CT and CT+TT carriers in T1DM group showed higher concentrations of serum glucose and glycated hemoglobin when compared with CC carriers. Conclusion: The LRP5 4037C>T may represent a candidate for T1DM susceptibility, as well as poor glycemic control.