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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2022

01-12-2022 | Scoliosis | Research

Delineation of dual molecular diagnosis in patients with skeletal deformity

Authors: Lian Liu, Liying Sun, Yujun Chen, Muchuan Wang, Chenxi Yu, Yingzhao Huang, Sen Zhao, Huakang Du, Shaoke Chen, Xin Fan, Wen Tian, Zhihong Wu, Guixing Qiu, Terry Jianguo Zhang, Nan Wu, Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study group

Published in: Orphanet Journal of Rare Diseases | Issue 1/2022

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Abstract

Background

Skeletal deformity is characterized by an abnormal anatomical structure of bone and cartilage. In our previous studies, we have found that a substantial proportion of patients with skeletal deformity could be explained by monogenic disorders. More recently, complex phenotypes caused by more than one genetic defect (i.e., dual molecular diagnosis) have also been reported in skeletal deformities and may complicate the diagnostic odyssey of patients. In this study, we report the molecular and phenotypic characteristics of patients with dual molecular diagnosis and variable skeletal deformities.

Results

From 1108 patients who underwent exome sequencing, we identified eight probands with dual molecular diagnosis and variable skeletal deformities. All eight patients had dual diagnosis consisting of two autosomal dominant diseases. A total of 16 variants in 12 genes were identified, 5 of which were of de novo origin. Patients with dual molecular diagnosis presented blended phenotypes of two genetic diseases. Mendelian disorders occurred more than once include Osteogenesis Imperfecta Type I (COL1A1, MIM:166200), Neurofibromatosis, Type I (NF1, MIM:162200) and Marfan Syndrome (FBN1, MIM:154700).

Conclusions

This study demonstrated the complicated skeletal phenotypes associated with dual molecular diagnosis. Exome sequencing represents a powerful tool to detect such complex conditions.
Appendix
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Metadata
Title
Delineation of dual molecular diagnosis in patients with skeletal deformity
Authors
Lian Liu
Liying Sun
Yujun Chen
Muchuan Wang
Chenxi Yu
Yingzhao Huang
Sen Zhao
Huakang Du
Shaoke Chen
Xin Fan
Wen Tian
Zhihong Wu
Guixing Qiu
Terry Jianguo Zhang
Nan Wu
Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study group
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2022
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-022-02293-x

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