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Open Access 01-12-2021 | Strabismus | Research

Expanding the phenotypic spectrum of mutations in LRP2: a novel candidate gene of non-syndromic familial comitant strabismus

Authors: Yue Wang, Xuejuan Chen, Tao Jiang, Yayun Gu, Xiaohan Zhang, Wenwen Yuan, Andi Zhao, Rui Li, Zijin Wang, Zhibin Hu, Hu Liu

Published in: Journal of Translational Medicine | Issue 1/2021

Abstract

Background

Comitant strabismus (CS) is a heterogeneous disorder that is a major contributing factor to unilateral childhood-onset visual impairment. Studies have confirmed that genetic factors play an important role in the development of CS. The aim of this study was to identify the genetic cause of non-syndromic familial CS.

Methods

Fourteen unrelated CS families were recruited for the study. Twelve affected and 2 unaffected individuals from a large four-generation family (CS08) were selected to perform whole genome-wide linkage analysis. Parallel whole-exome sequencing (WES) was conducted in the same family (9 patients and 1 unaffected member) and 31 additional CS cases from 13 other unrelated families. Sanger sequencing was used to determine whether any of the remaining variants co-segregated with the disease phenotype in the corresponding family.

Results

Based on linkage analysis, CS in family CS08 mapped to a novel region of 34.17 centimorgan (cM) on chromosome 2q22.3-2q32.1 between markers D2S151 and D2S364, with a maximum log odds (LOD) score of 3.54 (theta = 0) at D2S142. Parallel WES identified a heterozygous variant, LRP2 c.335 A > G (p.Q112R), located in such a linkage interval that completely co-segregated with the disease in the family. Furthermore, another novel heterozygous variant (c.7274A > G, p.D2425G) in LRP2 that co-segregated was detected in 2 additional affected individuals from another unrelated family by WES. Both variants are predicted to be damaging by PolyPhen-2, SIFT and MutationTaster, and were absent in 100 ethnically matched normal controls.

Conclusion

LRP2 is a novel candidate genetic cause of non-syndromic familial CS.

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Title: Expanding the phenotypic spectrum of mutations in LRP2: a novel candidate gene of non-syndromic familial comitant strabismus
Authors: Yue Wang
Xuejuan Chen
Tao Jiang
Yayun Gu
Xiaohan Zhang
Wenwen Yuan
Andi Zhao
Rui Li
Zijin Wang
Zhibin Hu
Hu Liu
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Strabismus
Strabismus
Published in: Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-021-03155-z

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