PUBLICATION
A 127 kb truncating deletion of PGRMC1 is a novel cause of X-linked isolated paediatric cataract
- Authors
- Jones, J.L., Corbett, M.A., Yeaman, E., Zhao, D., Gecz, J., Gasperini, R.J., Charlesworth, J.C., Mackey, D.A., Elder, J.E., Craig, J.E., Burdon, K.P.
- ID
- ZDB-PUB-210420-4
- Date
- 2021
- Source
- European journal of human genetics : EJHG 29(8): 1206-1215 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cataract/genetics*
- Cataract/metabolism
- Cataract/pathology
- Child
- Gene Deletion
- Humans
- Male
- Membrane Proteins/chemistry
- Membrane Proteins/genetics*
- Membrane Proteins/metabolism
- Pedigree
- Protein Binding
- Receptors, Progesterone/chemistry
- Receptors, Progesterone/genetics*
- Receptors, Progesterone/metabolism
- Sterol 14-Demethylase/metabolism
- Zebrafish
- PubMed
- 33867527 Full text @ Eur. J. Hum. Genet.
Citation
Jones, J.L., Corbett, M.A., Yeaman, E., Zhao, D., Gecz, J., Gasperini, R.J., Charlesworth, J.C., Mackey, D.A., Elder, J.E., Craig, J.E., Burdon, K.P. (2021) A 127 kb truncating deletion of PGRMC1 is a novel cause of X-linked isolated paediatric cataract. European journal of human genetics : EJHG. 29(8):1206-1215.
Abstract
Inherited paediatric cataract is a rare Mendelian disease that results in visual impairment or blindness due to a clouding of the eye's crystalline lens. Here we report an Australian family with isolated paediatric cataract, which we had previously mapped to Xq24. Linkage at Xq24-25 (LOD = 2.53) was confirmed, and the region refined with a denser marker map. In addition, two autosomal regions with suggestive evidence of linkage were observed. A segregating 127 kb deletion (chrX:g.118373226_118500408del) in the Xq24-25 linkage region was identified from whole-genome sequencing data. This deletion completely removed a commonly deleted long non-coding RNA gene LOC101928336 and truncated the protein coding progesterone receptor membrane component 1 (PGRMC1) gene following exon 1. A literature search revealed a report of two unrelated males with non-syndromic intellectual disability, as well as congenital cataract, who had contiguous gene deletions that accounted for their intellectual disability but also disrupted the PGRMC1 gene. A morpholino-induced pgrmc1 knockdown in a zebrafish model produced significant cataract formation, supporting a role for PGRMC1 in lens development and cataract formation. We hypothesise that the loss of PGRMC1 causes cataract through disrupted PGRMC1-CYP51A1 protein-protein interactions and altered cholesterol biosynthesis. The cause of paediatric cataract in this family is the truncating deletion of PGRMC1, which we report as a novel cataract gene.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping