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Genotypic Characterization of a Chinese Family with Osteogenesis Imperfecta and Generation of Disease-Specific Induced Pluripotent Stem Cells

Authors :
Dandan Li
Minglin Ou
Guandong Dai
Peng Zhu
Qi Luo
Jieping Chen
Zahir Shah
Igor M. Samokhvalov
Lianghong Yin
Guoping Sun
Donge Tang
Yong Dai
Source :
Frontiers in Bioscience-Landmark, Vol 28, Iss 12, p 336 (2023)
Publication Year :
2023
Publisher :
IMR Press, 2023.

Abstract

Background: Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by recurring bone fractures. Some OI patients have other clinical manifestations such as growth retardation, dental abnormalities, blue sclera, and hearing loss. The relationship between the phenotype and genotype of OI is indistinct, and there is no cure for OI. Therefore, an appropriate disease model is urgently needed to understand the pathophysiology of OI. Induced pluripotent stem cells (iPSCs) are capable of developing into three germ layers and have the same genetic background as the donor cells they were derived from; thus, they are an appropriate disease model. Methods: Blood samples collected from the proband and her affected children and one unaffected child were used forgenotyping by whole genome sequencing. A patient-specific iPSC line and a healthy donor iPSC line were generated by reprogramming peripheral blood mononuclear cells with episomal plasmids containing seven transcription factors, namely, OCT4, SOX2, NANOG, LIN28, cMYC, KLF4, and SV40LT. Results: The proband and her two affected children were homozygous for a mutation in collagen type I alpha 1 exon 10, c.725G>T, predicting a p.G242V substitution. A patient-specific iPSC line and a healthy donor iPSC line were generated and characterized in terms of their human embryonic stem cell-like morphology, expression of pluripotency markers, and the ability to differentiate into cells of three germ layers. Conclusions: Here, we report the phenotyping and iPSC disease modeling of an OI family. The detailed phenotyping of the OI family and establishment of iPSCs from an OI patient and healthy family member will provide a powerful tool to evaluate the pathophysiology of OI and develop targeted therapies.

Details

Language :
English
ISSN :
27686701
Volume :
28
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Frontiers in Bioscience-Landmark
Publication Type :
Academic Journal
Accession number :
edsdoj.37709c9ee85e4bbca8d8347007a17683
Document Type :
article
Full Text :
https://doi.org/10.31083/j.fbl2812336