Benedetto, Biglieri, Castellani, Digital Transmission Theory, Prentice-Hall, 1987 Appendix
Societe Francaise de la Mucoviscidose Journées annuelles, les 6 et 7 décembre 2007 CF Neonatal...
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Transcript of Societe Francaise de la Mucoviscidose Journées annuelles, les 6 et 7 décembre 2007 CF Neonatal...
Societe Francaise de la MucoviscidoseJournées annuelles, les 6 et 7 décembre 2007
CF Neonatal Screening in Europe
Carlo CastellaniVerona Cystic Fibrosis Center
years0 5 10 15 20 25 30 35
VenetoLeeds
East AngliaNorthamptonshi
LombardyTuscany
Northern IrelandSouth Yorkshire
MarcheWales
LiguriaSicily
Lazio 1Austria
Lazio 2 UmbriaCastilla-Leon
PolandPiedmontCatalunya
Emilia RomagnaFrance
ScotlandGalice
CalabriaSardinia
Czech Republic
CF NBS duration in Europe (2004)
CFNeonatalScreeningin Europe
6
13
1
3
11
ScreeningServices
(JCF 2007 6:57-65)
Infants screened for PKU and CF in 2004(ISNS data)
PKU 5,886,965
CF 1,622,651
non CFCF
Infants screened for PKU and CF in 2007(predicted)
EUROPE
PKU 6,000,000
CF 3,397,000
non CFCF
bIRTSWEATTEST
2 →
8 rIRT
2 MUT
14 rIRT / MUT
Protocols comparisonScreening
centersbIRT
μg/l
cutoff
(range)
bIRT
Centile
cutoff
(range)
rIRT
μg/l
cutoff
(range)
Mutation panel
detection rate
(range)
- 2 65
(60-70)
- - -
rIRT 8 57.5
(34-70)
99
(90-99)
36
(26-56)
-
MUT 2 65
(60-70)
- - 92.5
(90-95)
rIRT
MUT
14 70
(60-75)
99.1
(95-99.5)
55
(40-60)
82
(54-90)
Mutation panel detection rate
• Median 82%• lower interquartile
76.8%• higher interquartile
86.3%
0
1
2
3
4
5
6
% mutation-negative
76.8detectionrate82detectionrate86.3detectionrate
Protocols comparison
Screening centers
Years of screening
(min-max)
Neonates screened per
year
Incidence False negatives per year
- 2 4.4
(0.8-8)
12,500
(11000-14000)
- -
rIRT 8 5.5
(0.9-21)
29,250
(16000-80000)
1/4450
(1/2850-10500)
0.5
(0.29-0.86)
MUT 2 4
(0-8)
- - -
rIRT
MUT
*
13 9
(2-32)
33,000
(7900-9 2000)
1/2775
(1/2250-5200)
0.3
(0-1)
* France not included
0 5000 10000 15000 20000
carriernewbornsaffectednewbornssweat tests
IRTpositivenewborns
ScreenedNewborns1,659,400
IRTPos
17,223(1.03%)
SweatTests
(24 answers)3,111
(18.06%IRT+)
CF410
(13.17% ST2.38%IRT+)
Carriers(19 answers)
850
EUROPE:CF NBS EPIDEMIOLOGY (per year)
0
2
4
6
8
10
12
0 100
200
300
400
500
600
700
800
900
1000
0
10
20
30
40
50
60
70
80
90
100
0 100
200
300
400
500
600
700
800
900
1000
1100
1200
1300
1400
F508 carrier frequency according to IRT
concentrations
Cumulative frequency distribution of IRT in healthy F508 carriers ()
and F508 non-carriers (O)
F50
8 C
arri
er F
requ
ency
(%
)
IRT (g/L) IRT (g/L)
Cum
ulat
ive
Fre
quen
cy (
%)
adapted from: Lecoq I et al, Acta Pædiatr 88: 338-41, 1999.
10,000neonates
january 1995-
february1998
CFTRtesting
1078delT; 1609delCA; 1717-1g/a;1717-8g/a; 1898+3a/g; 2183aa/g;
2789+5g/a; 3849+10Kb; 394delTT;457TAT>G; 541delC;621+1g/t;711+1g/t; 711+5g/a; A559T;
deltaF508; deltaI507; G542X;G551D;
G85E; N1303K; Q552X; R1158X;R1162X; R117H; R334Q; R334W;R347H; R347P; R352Q; R553X;R709X; S549I; S549I; S549N;
S549Ra/c; T338I; W1282X
4 CF (1/2,500)
304 carriers (1/33)
9,692 negative(residual carrier
risk 1/180)
304 controlsCastellani C et al
Am J Med Genet 2005135A:142-4
0
20
40
60
80
100
120
140
IRTcentile 0-49 IRTcentile 50-85 IRTcentile >85
HETEROZYGOTES VS CONTROLSN
UM
BE
R O
F N
EO
NA
TE
S HETEROZYGOTES CONTROLS
Castellani C et al; Am J Med Genet 2005 135A:142-4
2040
6080
100
120
no y es
Tim
e fo
r dia
gnos
is
Mutations 2nd step
p 0.01
Conclusions
CF neonatal screening is growing in Europe
CF neonatal screening strategies are heterogeneous
CF birth prevalence changes considerably throughout Europe
Useful a monitoring system of data and results