Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out.
Multiple genes and their variants that lend susceptibility to many diseases will play a major role in clinical routine. Genetics-based cost reduction strategies in diagnostic processes are important in the setting of multiple susceptibility genes for a single disease. Head and neck paraganglioma (HNP) is caused by germline mutations of at least three succinate dehydrogenase subunit genes (SDHx). Mutation analysis for all 3 costs approximately US$2,700 per patient. Genetic classification is essential for downstream management of the patient and preemptive management of family members. Utilizing HNP as a model, we wanted to determine predictors to prioritize the most heritable clinical presentations and which gene to begin testing in HNP presentations, to reduce costs of genetic screening. Patients were tested for SDHB, SDHC, and SDHD intragenic mutations and large deletions. Clinical parameters were analyzed as potential predictors for finding germline mutations. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Of 598 patients, 30.6% had SDHx germline mutations: 34.4% in SDHB, 14.2% SDHC, and 51.4% SDHD. Predictors for an SDHx mutation are family history [odds ratio (OR), 37.9], previous pheochromocytoma (OR, 10.9), multiple HNP (OR, 10.6), age <or=40 years (OR, 4.0), and male gender (OR, 3.5). By screening only preselected cases and a stepwise approach, 60% cost reduction can be achieved, with 91.8% sensitivity and 94.5% negative predictive value. Our data give evidence that clinical parameters can predict for mutation and help prioritize gene testing to reduce costs in HNP. Such strategy is cost-saving in the practice of genetics-based personalized health care.
Neumann
Hartmut P H
HP
Department of Nephrology, Section of Preventive Medicine, Albert-Ludwigs University, Freiburg, Germany. hartmut.neumann@uniklinik-freiburg.de
Erlic
Zoran
Z
Boedeker
Carsten C
CC
Rybicki
Lisa A
LA
Robledo
Mercedes
M
Hermsen
Mario
M
Schiavi
Francesca
F
Falcioni
Maurizio
M
Kwok
Pingling
P
Bauters
Catherine
C
Lampe
Karen
K
Fischer
Markus
M
Edelman
Emily
E
Benn
Diana E
DE
Robinson
Bruce G
BG
Wiegand
Stefanie
S
Rasp
Gerd
G
Stuck
Boris A
BA
Hoffmann
Michael M
MM
Sullivan
Maren
M
Sevilla
Maria A
MA
Weiss
Marjan M
MM
Peczkowska
Mariola
M
Kubaszek
Agata
A
Pigny
Pascal
P
Ward
Robyn L
RL
Learoyd
Diana
D
Croxson
Michael
M
Zabolotny
Dmitry
D
Yaremchuk
Svetlana
S
Draf
Wolfgang
W
Muresan
Mihaela
M
Lorenz
Robert R
RR
Knipping
Stephan
S
Strohm
Michael
M
Dyckhoff
Gerhard
G
Matthias
Christoph
C
Reisch
Nicole
N
Preuss
Simon F
SF
Esser
Dirk
D
Walter
Martin A
MA
Kaftan
Holger
H
Stöver
Timo
T
Fottner
Christian
C
Gorgulla
Harald
H
Malekpour
Mahdi
M
Zarandy
Masoud Motasaddi
MM
Schipper
Jörg
J
Brase
Christoph
C
Glien
Alexander
A
Kühnemund
Matthias
M
Koscielny
Sven
S
Schwerdtfeger
Peter
P
Välimäki
Matti
M
Szyfter
Witold
W
Finckh
Ulrich
U
Zerres
Klaus
K
Cascon
Alberto
A
Opocher
Giuseppe
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Ridder
Gerd J
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Januszewicz
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D018095:Germ-Line Mutation; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000235:genetics*; D055815:Young Adult