Molecular diagnosis in a cohort of 114 patients with rare skeletal dysplasias.
Karina C SilveiraThatiane Y KanazawaCynthia SilveiraMaria D J Lacarrubba-FloresBenilton S CarvalhoDenise Pontes CavalcantiPublished in: American journal of medical genetics. Part C, Seminars in medical genetics (2021)
Molecular diagnosis is important to provide accurate genetic counseling of skeletal dysplasias (SD). Although next-generation sequencing (NGS) techniques are currently the preferred methods for analyzing these conditions, some of the published results have not shown a detection rate as high as it would be expected. The present study aimed to assess the diagnostic yield of targeted NGS combined with Sanger sequencing (SS) for low-coverage exons of genes of interest and exome sequencing (ES) in a series of patients with rare SD and use two patients as an example of our strategy. This study used two different in-house panels. Of 93 variants found in 88/114 (77%) patients, 57 are novel. The pathogenic variants found in the following genes: B3GALT6, PCYT1A, INPPL1, LIFR, of four patients were only detected by SS. In conclusion, the high diagnostic yield reached in the present study can be attributed to both a good selection of patients and the utilization of the SS for the insufficiently covered regions. Additionally, the two case reports-a patient with acrodysostosis related to PRKAR1A and another with ciliopathy associated with KIAA0753, add new and relevant clinical information to the current knowledge.
Keyphrases
- end stage renal disease
- ejection fraction
- newly diagnosed
- chronic kidney disease
- prognostic factors
- healthcare
- randomized controlled trial
- gene expression
- copy number
- genome wide
- single cell
- high resolution
- case report
- drug delivery
- mass spectrometry
- social media
- men who have sex with men
- hiv infected
- label free
- cell free
- hiv testing
- loop mediated isothermal amplification