Molecular diagnosis in a cohort of 114 patients with rare skeletal dysplasias.
KIAA0753 gene
PRKAR1A gene
exome sequencing
skeletal ciliopathy
skeletal dysplasia
targeted NGS
Journal
American journal of medical genetics. Part C, Seminars in medical genetics
ISSN: 1552-4876
Titre abrégé: Am J Med Genet C Semin Med Genet
Pays: United States
ID NLM: 101235745
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
31
08
2021
received:
22
06
2021
accepted:
07
09
2021
pubmed:
17
9
2021
medline:
16
10
2021
entrez:
16
9
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34529350
doi: 10.1002/ajmg.c.31937
doi:
Substances chimiques
B3GALT6 protein, human
EC 2.4.1.-
Galactosyltransferases
EC 2.4.1.-
Choline-Phosphate Cytidylyltransferase
EC 2.7.7.15
PCYT1A protein, human
EC 2.7.7.15
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
396-408Informations de copyright
© 2021 Wiley Periodicals LLC.
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