Analysis of LRP5 gene variants in a Chinese pedigree affected with Osteoporosis-pseudoglioma syndrome.
10.3760/cma.j.cn511374-20201125-00828
- Author:
Zhouxian BAI
1
;
Zhihui JIAO
;
Xiangdong KONG
Author Information
1. Genetics and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China. kongxd@263.net.
- Publication Type:Journal Article
- MeSH:
Aged;
China;
Humans;
Language;
Low Density Lipoprotein Receptor-Related Protein-5/genetics*;
Mutation;
Osteogenesis Imperfecta/genetics*;
Pedigree
- From:
Chinese Journal of Medical Genetics
2022;39(2):185-188
- CountryChina
- Language:Chinese
-
Abstract:
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.
