Author:
Zhang Shuang,Zhang Fangxia,Wang Juan,Yang Shangying,Ren Yinghua,Rui Xue,Xia Xiaobo,Sheng Xunlun
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.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Key Research and Development Project of Ningxia Hui Autonomous Region
Ningxia Natural Science Foundation
Key R&D Plan of Hunan Province of China
Cited by
3 articles.
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