Novel Compound Heterozygous Variations in MPDZ Gene Caused Isolated Bilateral Macular Coloboma in a Chinese Family

  • Cells. 2022 Nov 14;11(22):3602. doi: 10.3390/cells11223602.
Shuang Zhang  1  2 ,  Fangxia Zhang  1 ,  Juan Wang  3 ,  Shangying Yang  1 ,  Yinghua Ren  1 ,  Xue Rui  4 ,  Xiaobo Xia  2 ,  Xunlun Sheng  1  4
Affiliations
  • 1. People's Hospital of Ningxia Hui Autonomous Region (Ningxia Medical University Affiliated People's Hospital of Autonomous Region), Ningxia Eye Hospital, Ningxia Clinical Research Center on Diseases of Blindness in Eye, Yinchuan 750001, China.
  • 2. Eye Center of Xiangya Hospital, Hunan Key Laboratory of Ophthalmology, National Clinical Research Center for Geriatric Disorders of Xiangya Hospital Central South University, Changsha 410008, China.
  • 3. Department of Ophthalmology, Qingdao West Coast New District Central Hospital, Qingdao 266071, China.
  • 4. Gansu Aier Ophthalmology & Optometry Hospital, Lanzhou 730050, China.
PMID: 36429029 DOI: 10.3390/cells11223602
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.

Keywords
MPDZ; compound heterozygous mutation; ellipsoid zone; macular coloboma; retina.
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