Delineation of dual molecular diagnosis in patients with skeletal deformity

Autor: Lian Liu, Liying Sun, Yujun Chen, Muchuan Wang, Chenxi Yu, Yingzhao Huang, Sen Zhao, Huakang Du, Shaoke Chen, Xin Fan, Wen Tian, Zhihong Wu, Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study group, Guixing Qiu, Terry Jianguo Zhang, Nan Wu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Orphanet Journal of Rare Diseases, Vol 17, Iss 1, Pp 1-9 (2022)
Druh dokumentu: article
ISSN: 1750-1172
DOI: 10.1186/s13023-022-02293-x
Popis: 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.
Databáze: Directory of Open Access Journals
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