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.
Department of Nephrology, Section of Preventive Medicine, Albert-Ludwigs University, Freiburg, Germany. hartmut.neumann@uniklinik-freiburg.de
Hartmut P H
HP
Neumann
Zoran
Z
Erlic
Carsten C
CC
Boedeker
Lisa A
LA
Rybicki
Mercedes
M
Robledo
Mario
M
Hermsen
Francesca
F
Schiavi
Maurizio
M
Falcioni
Pingling
P
Kwok
Catherine
C
Bauters
Karen
K
Lampe
Markus
M
Fischer
Emily
E
Edelman
Diana E
DE
Benn
Bruce G
BG
Robinson
Stefanie
S
Wiegand
Gerd
G
Rasp
Boris A
BA
Stuck
Michael M
MM
Hoffmann
Maren
M
Sullivan
Maria A
MA
Sevilla
Marjan M
MM
Weiss
Mariola
M
Peczkowska
Agata
A
Kubaszek
Pascal
P
Pigny
Robyn L
RL
Ward
Diana
D
Learoyd
Michael
M
Croxson
Dmitry
D
Zabolotny
Svetlana
S
Yaremchuk
Wolfgang
W
Draf
Mihaela
M
Muresan
Robert R
RR
Lorenz
Stephan
S
Knipping
Michael
M
Strohm
Gerhard
G
Dyckhoff
Christoph
C
Matthias
Nicole
N
Reisch
Simon F
SF
Preuss
Dirk
D
Esser
Martin A
MA
Walter
Holger
H
Kaftan
Timo
T
Stöver
Christian
C
Fottner
Harald
H
Gorgulla
Mahdi
M
Malekpour
Masoud Motasaddi
MM
Zarandy
Jörg
J
Schipper
Christoph
C
Brase
Alexander
A
Glien
Matthias
M
Kühnemund
Sven
S
Koscielny
Peter
P
Schwerdtfeger
Matti
M
Välimäki
Witold
W
Szyfter
Ulrich
U
Finckh
Klaus
K
Zerres
Alberto
A
Cascon
Giuseppe
G
Opocher
Gerd J
GJ
Ridder
Andrzej
A
Januszewicz
Carlos
C
Suarez
Charis
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Eng
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