TY - JOUR
T1 - High-depth next-generation sequencing panel testing in the evaluation of arteriovenous malformations
AU - Hernandez, Patricia V.
AU - King, Katherine A.
AU - Evenson, Michael J.
AU - Corliss, Meagan M.
AU - Schroeder, Molly C.
AU - Heusel, Jonathan W.
AU - Neidich, Julie A.
AU - Cao, Yang
N1 - Funding Information:
The authors thank the patients and their families for contributing to this study. The authors also thank all faculty and staff at the genetic and genomic services at the Washington University in St. Louis.
Publisher Copyright:
© 2023 Wiley Periodicals LLC.
PY - 2023/6
Y1 - 2023/6
N2 - Arteriovenous malformations (AVMs) are vascular lesions in which an overgrowth of blood vessels of varying sizes develops with one or more direct connections between the arterial and venous circulation. We performed a retrospective review of a cohort of 54 patients with AVMs referred to our clinical genomic laboratory for high-depth next-generation sequencing (NGS) panel of Disorders of Somatic Mosaicism (DoSM). Thirty-seven of 54 patients were female (68.5%). Among the 54 cases, 37 (68.5%) cases had pathogenic and/or likely pathogenic (P/LP) variants identified, two cases (3.7%) had variants of uncertain clinical significance, and the remaining 15 cases (27.8%) had negative results. MAP2K1 variants were found in 12 cases, followed by eight cases with KRAS variants and seven with TEK variants, and the remainder being identified in several other genes on the panel. Among the 37 positive cases, 32 cases had somatic alterations only; the remaining five cases had at least one germline P/LP variant, including four cases with PTEN and one with RASA1. Of note, two cases had the unexpected co-existence of two P/LP variants. In summary, this study illustrated the molecular diagnostic yield (68.5%) of this cohort of patients with a clinical indication of AVMs by our high-depth DoSM NGS panel.
AB - Arteriovenous malformations (AVMs) are vascular lesions in which an overgrowth of blood vessels of varying sizes develops with one or more direct connections between the arterial and venous circulation. We performed a retrospective review of a cohort of 54 patients with AVMs referred to our clinical genomic laboratory for high-depth next-generation sequencing (NGS) panel of Disorders of Somatic Mosaicism (DoSM). Thirty-seven of 54 patients were female (68.5%). Among the 54 cases, 37 (68.5%) cases had pathogenic and/or likely pathogenic (P/LP) variants identified, two cases (3.7%) had variants of uncertain clinical significance, and the remaining 15 cases (27.8%) had negative results. MAP2K1 variants were found in 12 cases, followed by eight cases with KRAS variants and seven with TEK variants, and the remainder being identified in several other genes on the panel. Among the 37 positive cases, 32 cases had somatic alterations only; the remaining five cases had at least one germline P/LP variant, including four cases with PTEN and one with RASA1. Of note, two cases had the unexpected co-existence of two P/LP variants. In summary, this study illustrated the molecular diagnostic yield (68.5%) of this cohort of patients with a clinical indication of AVMs by our high-depth DoSM NGS panel.
KW - arteriovenous malformations
KW - next-generation sequencing
KW - somatic mosaicism
UR - http://www.scopus.com/inward/record.url?scp=85150758911&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.63171
DO - 10.1002/ajmg.a.63171
M3 - Article
C2 - 36924216
AN - SCOPUS:85150758911
SN - 1552-4825
VL - 191
SP - 1518
EP - 1524
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 6
ER -