CYP17A1 Pathogenic Variants in 26 Chinese Patients With 17α-Hydroxylase Deficiency by Targeted Long-Read Sequencing
Authors' conclusion
The TLRS can determine the cis/trans orientation of 2 distant variants. Five novel pathogenic variants were reported, broadening the spectrum of the CYP17A1 pathogenic variants. The variant c.866A > G, located deep in the exon, affects gene function through mechanisms of aberrant splicing.
Study context
- Population
- Chinese patients with 17α-hydroxylase/17,20-lyase deficiency (17-OHD)
- Participants
- 26 patients
- Outcome
- CYP17A1 pathogenic variants
Methodological detailstargeted long-read sequencing, minigene splicing assays, ACMG classification
- Targeted long-read sequencing
- Minigene splicing assays
- ACMG classification
Main finding
As reported in the abstract
- Trans pathogenic variants detected per patient by targeted long-read sequencing (TLRS)
- 2
- Pathogenic variants in CYP17A1 identified
- 20
- c.985_987delinsAA, most frequent variant
- 28/52 alleles
- c.1459_1467del, second most frequent
- 4/52 alleles
- Novel variants (c.280T > C, c.470T > A, c.636_637del, c.866A > G, c.1095del) classified pathogenic/likely pathogenic by ACMG
- 5
Observational data: associations, not effects.
Further findings
Minigene splicing assays
- c.866A > G in exon 5 causes frameshift due to 104 base pair deletion
- c.470T > A generates 2 transcripts: vast majority spliced like wild-type, small fraction lacking 35 base pairs in 5' flank of exon 3
Original publication
CYP17A1 Pathogenic Variants in 26 Chinese Patients With 17α-Hydroxylase Deficiency by Targeted Long-Read Sequencing. J Clin Endocrinol Metab. Published 27 June 2024. doi:10.
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