Molecular diagnosis in a cohort of 114 patients with rare skeletal dysplasias

Autor(es)

Silveira, Karina C. ^[1] ; Kanazawa, Thatiane Y. ^[1] ; Silveira, Cynthia ^[1] ; Lacarrubba-Flores, Maria D. J. ^[1] ; Carvalho, Benilton S. ^[2] ; Cavalcanti, Denise P. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Med Genet, Dept Translat Med, Skeletal Dysplasias Grp, Campinas - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Inst Math Stat & Sci Comp, Dept Stat, Campinas - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS; v. 187, n. 3, SI SEP 2021.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 98/16006-6 - Estudo da etiopatogenia dos defeitos congênitos de alta morbi-mortalidade no período perinatal
• Beneficiário: Denise Pontes Cavalcanti
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/22145-6 - Contribuição ao estudo clínico-etiológico das displasias esqueléticas e disostoses no Brasil
• Beneficiário: Denise Pontes Cavalcanti
• Modalidade de apoio: Auxílio à Pesquisa - Regular