PUBLICATION
Novel Compound Heterozygous Variations in MPDZ Gene Caused Isolated Bilateral Macular Coloboma in a Chinese Family
- Authors
- Zhang, S., Zhang, F., Wang, J., Yang, S., Ren, Y., Rui, X., Xia, X., Sheng, X.
- ID
- ZDB-PUB-221127-4
- Date
- 2022
- Source
- Cells 11(22): (Journal)
- Registered Authors
- Keywords
- MPDZ, compound heterozygous mutation, ellipsoid zone, macular coloboma, retina
- MeSH Terms
-
- Animals
- China
- Coloboma*/genetics
- Coloboma*/pathology
- PDZ Domains*
- Zebrafish/genetics
- PubMed
- 36429029 Full text @ Cells
Citation
Zhang, S., Zhang, F., Wang, J., Yang, S., Ren, Y., Rui, X., Xia, X., Sheng, X. (2022) Novel Compound Heterozygous Variations in MPDZ Gene Caused Isolated Bilateral Macular Coloboma in a Chinese Family. Cells. 11(22):.
Abstract
Macular coloboma (MC) is a rare congenital retinochoroidal defect characterized by lesions of different sizes in the macular region. The pathological mechanism underlying congenital MC is unknown. Novel compound heterozygous variations, c.4301delA (p.Asp1434fs*3) and c.5255C>G (p.Ser1752Ter), in the multiple PDZ domain (MPDZ) proteins were identified via whole-exome analysis on the proband with isolated bilateral macular coloboma in a Chinese family. Segregation analysis revealed that each of the unaffected parents was heterozygous for one of the two variants. The results of the in silico and bioinformatics analysis were aligned with the experimental data. The knockdown of MPDZ in zebrafish caused a decrease in the ellipsoid zone, a destruction of the outer limiting membrane, and the subsequent RPE degeneration. Overall, the loss of MPDZ in zebrafish contributed to retinal development failure. These results indicate that MPDZ plays an essential role in the occurrence and maintenance of the macula, and the novel compound heterozygous variations were responsible for an autosomal recessive macular deficiency in this Chinese family.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping