Variation phénotypique et moléculaire des hémoglobinopathies en

133
Variation phénotypique et moléculaire des hémoglobinopathies en milieu
carcinologique
Abaza H., Gara Y., Ben Chaabene A., Douik H., Harzallah L.,
Boussen H., Guemira F.
+/@7/B7=< >6L<=BG>7?C3 3B ;=:L1C:/7@3 23A 6L;=5:=07<=>/B673A 3<
;7:73C1/@17<=:=57?C3
!)*#("!+=:<R
Pré-requis: !3A /<=;/:73A 23 :V6L;=5:=07<3 A3 27D7A3<B 3<
/<=;/:73A ?C/:7B/B7D3A 3B /<=;/:73A ?C/<B7B/B7D3A 3A D/@7/<BA
1=;>=@B3<B23A>=:G;=@>67A;3AA=CD3<BCB7:3A1=;;3;/@?C3C@A23
>=>C:/B7=< 1BC3::3;3<B >:CA 23  BG>3A 2V6L;=5:=07<3A
/<=@;/:3A A=<B @L>3@B=@7LA 3A 6L;=5:=07<=>/B673A >3CD3<B
AC@D3<7@163H23AAC83BA/BB37<BA23>/B6=:=573A1/<1L@3CA3A
But : '/>>=@B3@:3A/AA=17/B7=<A6L;=5:=07<=>/B673A1/<13@A#=B@3
LBC23 / LBL @L/:7AL3 I :V<AB7BCB (/:/6 H/PH ( 1=<13@</<B :3A
6L;=5:=07<=>/B673A 3< ;7:73C 1/@17<=:=57?C3 AC@ C<3 >L@7=23
AVLB/:/<B2C;=7A23"/7/C;=7A23LD@73@
Méthodes : !VLBC23>6L<=BG>7?C33B07=167;7?C323:V6L;=5:=07<3
/@LDL:L:/>@LA3<1323>=@B3C@A2V/<=;/:73A23:V6L;=5:=07<3
AC@C<B=B/:23>/B73<BAAC7D7AI:V(BG>3A2V/<=;/:73A23
:V6L;=5:=07<3=<BLBL723<B747LA0(00$/@/000
;CB/<B@/>7233BSB6/:/AAL;73
Résultats : !3B@/7B 2@L>/<=1GB/7@3@3>@LA3<B3 :V6L;=5:=07<=>/B673
:/>:CA@L>/<2C323AAC83BA>=@B3C@A2V/<=;/:73A23
:V6L;=5:=07<3A=<BAC7D7A>=C@23A>/B6=:=573A;/:75<3A%/@;713A
6L;=5:=07<=>/B673A=</@LDL:L:/>@LA3<132323CF;CB/<BA@/>723A
23:V6L;=5:=07<31=@@3A>=<2/<BI:V6L;=5:=07<3/<59=93BG>3
23 ;CB/<B @/@3 3AB 2L1@7B >=C@ :/ >@3;7M@3 4=7A 3< )C<7A73 (3:=<
:VLBC235L<=BG>7?C32313A23CF1/A:V6L;=5:=07<3/<59=9@LAC:B3
23:/AC0AB7BCB7=</C<7D3/C23:/16/O<3S23:V/1723/A>/@B7?C3>/@
:/5:G17<3AC7B3IC<3;CB/B7=</C<7D3/C2C1=2=< *<3LBC23
>6L<=BG>7?C34/;7:7/:3/@LDL:L:/>@LA3<1323;CB/B7=<AA7;7:/7@3A
163H13@B/7<A;3;0@3A23:/4/;7::3
Conclusion : #=B@3B@/D/7:<=CA/>3@;7A231=<AB/B3@C<34@L?C3<13
@3:/B7D3;3<B 7;>=@B/<B3 2V/<=;/:73A @/@3A 23 :V6L;=5:=07<3 163H
23A;/:/23A>@LA3<B/<B23A>@=13AACABC;=@/CFD/@7LA
L;=5:=07<=>/B673A 1/<13@ 6L;=5:=07<3 /<59=9 LBC23
;=:L1C:/7@3
Abaza H., Gara Y., Ben Chaabene A., Douik H., Harzallah L.,
Boussen H., Guemira F.
%63<=BG>71/<2;=:31C:/@16/<53A=463;=5:=07<=>/B673A7<1/<13@
!)*#("!+=:<R
Background: )63 /0<=@;/:7B73A =4 B63 6/3;=5:=07< 27D723 7<B=
?C/:7B/B7D3/0<=@;/:7B73A/<2?C/<B7B/B7D3/0<=@;/:7B73A)67AD/@7/<B
1=<B/7<A >=:G;=@>67A;A =4B3< CA34C: /A ;/@93@A =4 >=>C:/B7=<B
>@3A3<B ;=@3 B6/<  BG>3A =4 /0<=@;/: 6/3;=5:=07< /@3 :7AB32
)67A63;=5:=07<=>/B673A1/</@7A3/B@3/1632AC0831BA=41/<13@=CA
>/B6=:=573A
Aim: )=0@7<5B=@3>=@B/AA=17/B7=<6L;=5:=07<=>/B673A1/<13@A
Methods: $C@ABC2GE/A@3/:7H32B=B63<AB7BCB3(/:/6/H/7H(
1=<13@<7<56L;=5:=07<=>/B673A7<1/@17<=:=5713<D7@=<;3<B=D3@/
>3@7=2A>@3/27<5=CB=4"/G7<30@C/@G)63>63<=BG>71
/<207=163;71/:ABC2G=46/3;=5:=07<@3D3/:32B63>@3A3<13=4
1/@@73@A =4 /0<=@;/:7B73A =4 B63 6/3;=5:=07< =< / B=B/: =4 
>/B73<BA 4=::=E32 B= (  BG>3A =4 /0<=@;/:7B73A =4 B63
6/3;=5:=07<E3@3723<B747320(00$/@/000
4/AB;CB/<B/<2SB6/:/AA3;7/
Results: )63 A719:3 13:: :7<3 @3>@3A3<BA B63 ;=AB E723A>@3/2
6L;=5:=07<=>/B673     =4 B63 1/@@73@ AC0831BA =4
/0<=@;/:7B73A =4 B63 6/3;=5:=07< /@3 4=::=E32 4=@ ;/:75</<B
>/B6=:=573A ;=<5 B63A3 63;=5:=07<=>/B673A E3 @3D3/:32 B63
>@3A3<13=4 BE=4/AB;CB/<BA=4B63 6/3;=5:=07<1=@@3A>=<27<5 B=
B636/3;=5:=07</<59=9)67ABG>3=4@/@3;CB/<B7A23A1@70324=@
B6347@ABB7;37<)C<7A7/11=@27<5B=B6353<=BG>71ABC2G0GB63A3
BE=1/A3AB636/3;=5:=07</<59=9@3AC:BA4@=;B63@3>:/13;3<B/B
B63:3D3:=4B6316/7<SA=;3/A>/@B71/1720GB63E7AB3@7/4C@B63@B=
/ B@/<A43@ /B B63 :3D3: =4 B63 1=2=<  >63<=BG>71 ABC2G 4/;7:G
@3D3/:32B63>@3A3<13=4A7;7:/@B@/<A43@A/B13@B/7<;3;03@A=4B63
4/;7:G
Conclusion: $C@ E=@9 /::=E32 CA B= <=B713 / @3:/B7D3:G 7;>=@B/<B
4@3?C3<1G =4 @/@3 /0<=@;/:7B73A =4 B63 6/3;=5:=07< /B >/B73<BA
>@3A3<B7<5D/@732BC;=@/:>@=13AA3A
3;=5:=07<=>/B673A 1/<13@ 6/3;=5:=07< /<59=9 ;=:31C:/@
ABC2G
0/H//83@/@/-=A@3<6//03<3@78=C79/G3B/@H/::/6!/B74/=CAA3</;=C2/C3;7@/3B67
*- Service de Biologie Clinique
**- Service de Médecine. Institut Salah Azaiz, Tunis, Tunisie
Faculté de médecine de Tunis, Université Tunis El Manar
ARTICLE ORIGINAL

Abaza H. - Variation phénotypique et moléculaire des hémoglobinopathies
134
!3A6L;=5:=07<=>/B673AA=<B23A/<=;/:73A6L@L27B/7@3A23
5:=0C:3 @=C53 @LAC:B/<B 2VC<3 /<=;/:73 23 AB@C1BC@3 =C 23
AG<B6MA3A7L53/<BAC@:3A16/O<3A235:=07<3:AV/57B2VC<3
>/B6=:=5736LBL@=5M<3/CF<7D3/CF1:7<7?C3A07=:=57?C3A3B
;=:L1C:/7@3A/::/<B23A4=@;3AB=B/:3;3<B/AG;>B=;/B7?C3A
/CF4=@;3A:3A>:CA5@/D3A!/4@L?C3<13:/27AB@70CB7=<23A
6L;=5:=07<=>/B673A 2/<A :3 ;=<23 3B :3A ;=G3<A
B6L@/>3CB7?C3A 3<1=@3 :7;7BLA 4=<B 23A 13A /<=;/:73A C<
DL@7B/0:3 >@=0:M;3 23 A/<BL >C0:7?C3 *<3
6L;=5:=07<=>/B673  >3CB NB@3 @3<1=<B@L3 2/<A >:CA73C@A
4=@;3A 5L<LB7?C3;3<B D/@7L3A : >3CB AV/57@ 23A 4=@;3A
6LBL@=HG5=B3A 6=;=HG5=B3A 2=C0:3 6LBL@=HG5=B3 =C C<3
2=C0:3 /AA=17/B7=< 2V6L;=5:=07<=>/B673A 2744L@3<B3A !3
>@=0:M;3>3CBA327D3@A7473@2/D/<B/533B=<>3CBB@=CD3@23A
/AA=17/B7=<A 2V6L;=5:=07<=>/B673A /D31 2V/CB@3A ;/:/273A
5L<LB7?C3A1=<2C7A/<BI23AAG<2@=;3A>:CA/C;=7<A5@/D3A
A3:=< :3A 7<27D72CA  %:CA @L13;;3<B 3B /D31 :3
2LD3:=>>3;3<B 23A ;=G3<A 27/5<=AB7?C3A 7: 3AB 23D3<C
>=AA70:3 23 ;3BB@3 3< LD723<13 C<3 6L;=5:=07<=>/B673 3<
/AA=17/B7=< /D31 2V/CB@3A >/B6=:=573A /1?C7A3A /C 1=C@A
2V/</:GA3AGABL;/B7?C32CA/<52VC<;/:/23=C2CA/<5?C7D/
:C7 NB@3 B@/<A4CAL /<A :3 >@LA3<B B@/D/7: <=CA @/>>=@B=<A
:V/AA=17/B7=<23A6L;=5:=07<=>/B673A/D31:31/<13@
M AT E R I E L E T M E T H O D E S
A) Matériel 8:
/<A:/>@3;7M@3>/@B7323<=B@3B@/D/7:<=CA<=CAA=;;3A
7<BL@3AALA I :VLBC23 >6L<=BG>7?C3 23 :V6L;=5:=07<3 23A
>/B73<BAAC7D7A I:V<AB7BCB (/:/6H/7H ( 23)C<7A>=C@
>@=13AACABC;=@/:AC@C<3>L@7=23AVLB/:/<B2C;=7A23"/7
 /C ;=7A 23 LD@73@  )=CA :3A >@L:MD3;3<BA
>/@D3<CA=C>@L:3DLA/C:/0=@/B=7@3A=<B@31C37::7AAC@)
3B =<B AC07 C<3 LBC23 6L;/B=:=57?C3 6L;=5@/;;3 3B C<3
LBC2307=167;7?C323:V6L;=5:=07<3%=C@:3AAC83BAAC7D7A
>=C@C<>@=13AACA;/:7<:V=@757<35L=5@/>67?C33B:/</BC@3
23:/BC;3C@=<BLBL>@L17AL3A
/<A :/ M;3 >/@B73 <=CA<=CA A=;;3A 7<BL@3AALA/C 1/A23
23CF >/B73<B3AT  :VC<3 J5L3 23  /<A AC7D73 >=C@
/2L<=470@=;32CA37<3B:V/CB@3J5L323/<AAC7D73>=C@
1/@17<=;31/</:/7@37<47:B@/<B2CA37<%=C@13A23CF>/B73<BA
<=B@3 LBC23  / 1=;>=@BL 23CF />>@=163AT  C<3 />>@=163
>6L<=BG>7?C33BC<3/CB@35L<LB7?C3
B) Méthodes 8:
/BC236L;/B=:=57?C3T
>/@B7@2CA/<5>@L:3DLAC@)C<3<C;L@/B7=<A/<5C7<3/
LBL @L/:7AL3 1=;>=@B/<BT :3 B/CF 2V6L;=5:=07<3 3< 52: :3
<=;0@3235:=0C:3A@=C53A'3<';;:3<=;0@323
5:=0C:3A0:/<1A3<;;!3B/CF2V6L;/B=1@7B33<
BC<3<C;L@/B7=<23A>:/?C3BB3A
0 BC23 07=167;7?C3 23 :V6L;=5:=07<3T 1=;>=@B/<B C<3
L:31B@=>6=@MA3I>/:1/:7<C<33:31B@=>6=@MA3I>/17233B
C<2=A/5323:V0
1BC235L<LB7?C3
#=CA<=CA>@=>=A=<A2V/</:GA3@:3A/<=;/:73AAB@C1BC@/:3A
23:V023A23CF>/B73<BA>@L1L23;;3<B17BL3A
!3 0CB 23 13BB3 LBC23  3AB 2VLBC273@ :3 5M<3 0 23 13A 23CF
>/B73<B3A163H:3A?C3::3A:VLBC23L:31B@=>6=@3B7?C3/ @LDL:L
:V3F7AB3<1323;CB/<BA@/>723A23:V6L;=5:=07<3
#=CA/D=<A3FB@/7B2V/0=@223:V#5L<=;7?C3I>/@B7@2VC<
>@L:MD3;3<B  2C A/<5 B=B/: AC@ C< BC03 ) >/@ ;LB6=23
>6L<=: 16:=@=4=@;3 >@MA <=CA /D=<A 2LB3@;7<L :3A
1=<13<B@/B7=<A23 13B# >/@ A>31B@=A1=>73 IC<3 23<A7BL
=>B7?C3 23  <; !3 5L<=BG>/53 23 13A 7<27D72CA / LBL
34431BCL>/@:/B316<=:=57323%'AL?C3<K/53
R E S U LTAT S
!VLBC23>6L<=BG>7?C323A>/B73<BAAC7D7A/:V(23)C<7A/
1=<13@<LAC83BA/2C:B3A3BB3LBC23/@LDL:LC<B=B/:23
 >=@B3C@A 2V/<=;/:73A 23 :V0  3A ;/:/23A A3
@L>/@B7AA3<B3<6=;;3A3B43;;3A/D31C<A3F@/B7=
233A>/B73<BAA=<BAC7D7A2/<A1/A>=C@
23A>/B6=:=573A0L<75<3A3B2/<A1/A>=C@23A
BC;3C@A;/:75<3ACB=B/:A3>BBG>3A2V/<=;/:73A23:V0
=<BLBL723<B747LA0($/@/030;CB/<BA@/>723A
3B B6/:/AAL;73A)=CB3A 13A /<=;/:73A A3 B@=CD3<B / :VLB/B
6LBL@=HG5=B3A/C4C<A3C:1/A232@L>/<=1GB=A36=;=HG5=B3
((B/0:3/C!3AAC83BA1/<1L@3CFA3@L>/@B7AA3<B3<
6=;;3A3B43;;3A!/@L>/@B7B7=<23A
BG>3A2V/<=;/:73A23:V0163H:3A1/<1L@3CF3AB@3>@LA3<BL3
2/<A:3B/0:3/C!/@L>/@B7B7=<23A6L;=5:=07<=>/B673A
A3:=<:3BG>3231/<13@3AB@3>@LA3<BL31=;;31V3AB7<27?CL
2/<A:3B/0:3/C
Type d’anomalie
(
$
"CB/<B@/>723
((
XB6/:/AAL;73;7<3C@3
)=B/:
Nombre de sujets
porteurs d’anomalies
Pourcentage (%)
Tableau 1 : @L?C3<1323A/<=;/:73A23:V0
Type d’anomalie
(
$
"CB/<B@/>723
((
XB6/:/AAL;73;7<3C@3
)=B/:
Nombre de sujets
porteurs d’anomalies
Pourcentage (%)
Tableau 2 : %=C@13<B/5323A/<=;/:73A23:V0163H:3A1/<1L@3CF

LA TUNISIE MEDICALE - 2013 ; Vol 91 (n°02)
135
Etude des deux cas porteurs de mutant rapi de de l’Hb8:
#=CA <=CA A=;;3A 7<BL@3AALA I :VLBC23 >6L<=BG>7?C3 3B
;=:L1C:/7@323A23CF>/B73<B3A>=@B3CA3A23;CB/<B@/>723I
:VLB/B 6LBL@=HG5=B3 !/ >/B73<B3 <R J5L3 23  /<A A/<A
/<BL1L23<BA>/@B71C:73@A/LBL=>L@L3I@3>@7A3A3<3B
 >=C@ <=2C:3A ;C:B7>:3A @L1727D/<B3A 23A 23CF A37<A
!V3F/;3</</B=;=>/B6=:=57?C3/1=<1:CIC</2L<=470@=;3
A/<A A75<3A 23 ;/:75<7BLA %=C@ 13BB3 >/B73<B3 C<3 LBC23
4/;7:7/:3/LBL@L/:7AL3
!3A2=<<L3A@31C37::73AA=<B@3>@LA3<BL3A1723AA=CAT
!3AAC83BA+3B+A=<B/BB37<BA2V/2L<=470@=;32CA37<)=CA
:3A/CB@3A;3;0@3A23:/4/;7::3A=<B1:7<7?C3;3<BA/7<A
!/>/B73<B3<RJ5L323/<AAC7D73I:V(23>C7A/<A
>=C@1/@17<=;31/</:/7@37<47:B@/<B5/@23('2CA37<2@=7B
A=C;7AIC<B@/7B3;3<B1=<A3@D/B3C@/D31167;7=B6L@/>73
!3A>/@/;MB@3A6L;/B=:=57?C3A@31C37::7A>/@:V6L;=5@/;;3
;=<B@3<B?C3:3AAC83BA>@L:3DLA<3>@LA3<B3<B/C1C<3/<L;73
=C /CB@3/<=;/:736L;/B=:=57?C3!/ 475C@3 @3>@LA3<B3:/
;=07:7BL L:31B@=>6=@LB7?C3 23A 6L;=5:=07<3A AC@ 53:
2V/5/@=A3 I>/:1/:7<23AAC83BA >@L:3DLA !3A @LAC:B/BA23
:VLBC23L:31B@=>6=@3B7?C3A=<B@3>@LA3<BLA2/<A:3B/0:3/C
!VLBC23;=:L1C:/7@3/LBL:7;7BL3I:VLBC232C5M<30163H:3A
>/B73<B3A!VLBC23>6L<=BG>7?C3/;=<B@L:V3F7AB3<132VC<3
/<=;/:7323AB@C1BC@323:/16/O<305:=07<3
!35M<303AB:3A7M5323>:CA73C@A;CB/B7=<A/C<7D3/C2313A
@L57=<A 3F=<7?C3A #=CA /D=<A 2=<1 >@=1L2L I
:V/;>:7471/B7=<23AB@=7A3F=<A/C<7D3/C23135M<323VD3@A
V
!3A1=C>:3A2V/;=@13ACB7:7ALA>=C@16/?C3@L57=<2C5M<3S
/;>:747L3A=<B@3>@LA3<BLA2/<A:3B/0:3/C
!/2753AB7=<3<HG;/B7?C323:V3F=<3B/@LDL:L:/>@LA3<13
2VC<3 A3C:3 0/<23 23 B/7::3  >0  7: AV/57B 2VC< 4@/5;3<B
<=<275L@L?C71=@@3A>=<2/C 5M<3 S;CBLC <7D3/C23 13
5M<3S
!/AC0AB7BCB7=</C<7D3/C 2C1=2=<  23:V3F=< 3AB
B@/2C7B3  >/@ :3 @3;>:/13;3<B 23 :/ 5:G17<3 >/@ :V/1723
/A>/@B7?C3 : AV/57B 073< 2VC< 5M<3 S /<59=9 3BB3
;CB/B7=< 3AB@3B@=CDL3I:VLB/B6LBL@=HG5=B3 163H :3A 23CF
>/B73<B3A
!3 >@=47: 23 AL?C3<K/53 23 :V3F=<  / ;=<B@L :V3F7AB3<13
2VC<3AC0AB7BCB7=<3B/C<7D3/C2C1=2=<2C5M<3
S3BB3;CB/B7=<A3B@/2C7B>/@:/AC0AB7BCB7=<2C;N;3/1723
/;7<LT:/:3C17<3)):AV/57B2=<12VC<3;CB/B7=<
A7:3<173CA3?C73F7AB3I:VLB/B6=;=HG5=B3163H:/>@3;7M@3
>/B73<B33BI:VLB/B6LBL@=HG5=B3163H:/23CF7M;3>/B73<B3
B/0:3/C
D I S C U S S I O N
#=B@3LBC23232L>7AB/5323A/<=;/:73A23:V6L;=5:=07<3/
>=@BL AC@  >/B73<BA 23 :V(  23 )C<7A 3B / @LDL:L :/
>@LA3<1323>=@B3C@A2V6L;=5:=07<=>/B673A%/@;713A
>/B73<BA  ;/:/23A  A=<B AC7D7A >=C@ >@=13AACA
1/<1L@3CF !/ >@LD/:3<13 5:=0/:3 23A 6L;=5:=07<=>/B673A
163H:3AAC83BAAC7D7AI:V(3ABI23!/2@L>/<=1GB=A3
6LBL@=HG5=B3 3AB :V/<=;/:73>@L2=;7</<B3 2/<A<=B@3 AL@73
Figure 1 : 'L>/@B7B7=<2C<=;0@323@LD37:A<=1BC@<3A
Type de tumeur
/<13@2CA37<
/<13@2C>=C;=<
/<13@A2753AB74A
!G;>6=;3;/:7<<=<6=2597<73<
=ABL=A/@1=;3
/<13@23:/>3/C
/<13@AC@=:=57?C3A
/<13@A$'!
"/:/273236=2597<
/<13@A5G<L1=:=57?C3A
$@757<37<2LB3@;7<L3
)C;3C@A@/@3A
A/S
A/C A/D
A/O A/mutant rapide S/S β thal total A/G
Tableau 3 : 'L>/@B7B7=<23A6L;=5:=07<=>/B673AA3:=<:3BG>3231/<13@
Sujets
+
+>/B73<B3<R
+
%/B73<B3<R
Hb A%
Hb A2 % Mutant rapide %
Tableau 4 : &C/<B7471/B7=<A23A2744L@3<B3A4@/1B7=<A6L;=5:=07<7?C3A

Abaza H. - Variation phénotypique et moléculaire des hémoglobinopathies
136
23:V3<A3;0:323A1/A2L>7ABLA3B23A1/<1L@3CF
@38=75<3<B :3A 2=<<L3A 23 :/ :7BBL@/BC@3 >C7A?C3 :/
2@L>/<=1GB=A3 3AB :V6L;=5:=07<=>/B673 :/ >:CA @L>=<2C3
2/<A :3 ;=<23   !V0 ( 3AB /CAA7 :3 D/@73<B :3 >:CA
4@L?C3<B3<)C<7A73
/<A<=B@3LBC23:/0B6/:/AAL;73D73<B3<A31=<2@/<5/D31
C<34@L?C3<1323163H:V3<A3;0:323A;/:/23A3B
163H:3A1/<1L@3CF<4@7?C32C<=@2:3A>@LD/:3<13A23:/
0B6/:/AAL;73A=<B233<"/C@7B/<73/C"/@=1
3<:5L@733B3<B@33B3<!70G3
!V6L;=5:=07<=A3 6LBL@=HG5=B3 =11C>3 :/M;3 >:/13 2/<A
<=B@3AL@732/<A:V3<A3;0:323A;/:/23A3B163H
:3A 1/<1L@3CF 3BB3 /<=;/:73 3AB 1:/AAL3 :/ A31=<23 3<
4@7?C3AC@B=CB2/<A:V4@7?C323:V$C3AB/D31C<3>@LD/:3<13
;/F7;/:323/C"/:7
!VL;=5:=07<3 $ /@/0 3AB C< D/@7/<B >3C 4@L?C3<B 2/<A :3
;=<23  (/ >@LD/:3<13 2/<A <=B@3 AL@73 3AB 23 
163HB=CA:3A>/B73<BALBC27LA3B23163H:3A1/<1L@3CF
!V0  3AB C<3 /<=;/:73 @/@3 2/<A <=B@3 AL@73T   1/A A=7B
 23A 1/A 2L>7ABLA 2=<B  /BB37<B 23 >/B6=:=573
1/<1L@3CA3!/4@L?C3<132313BB3/<=;/:733AB4/70:33<!70G3
3B3<)C@?C73
/<A <=B@3 LBC23 :3 B@/7B 2@L>/<=1GB/7@3 @3>@LA3<B3
:V6L;=5:=07<=>/B673 :/ >:CA 4@L?C3<B3 163H :/ >:C>/@B 23A
1/<1L@3CF A/C4 13CF /BB37<BA 23 :/ ;/:/273 2V6=2597< 23
1/<13@2C>=C;=<1/<13@2753AB74A3BBC;3C@A@/@3A=Q:3B@/7B
2@L>/<=1GB/7@33AB;/8=@7B/7@3
/<A <=B@3 AL@73 >@MA 23  23A AC83BA A=<B /BB37<BA 23
1/<13@2CA37<D73<<3<B3<AC7B3:3A1/<13@A5G<L1=:=57?C3A
 >C7A 2753AB74A  3B$'! %:CA73C@A
LBC23A@/>>=@B3<B:V3F7AB3<13:/1=3F7AB3<132@L>/<=1GB=A3
1/<13@163HC<;N;37<27D72C47<232LB3@;7<3@:V7<1723<13
23 1/<13@ 3B :3 B/CF 23 ;=@B/:7BL  >/@ 1/<13@ 163H :3A
2@L>/<=1GB/7@3A /CF *( /E97< 3B /:  =<B @L/:7AL C<3
LBC23 AVLB/:/<B AC@ C<3 >L@7=23 23  /<A 23  / 
7<BL@3AA/<B  >/B73<BA /BB37<BA 23 2@L>/<=1GB=A3 %/@;7
13A>/B73<BA=<B2LD3:=>>LC<1/<13@2C@/<B13BB3>L@7=23
Etude mo l écul ai re
!35M<3S1=2/<B>=C@:/AG<B6MA323:/16/O<3S5:=07<33AB
:=1/:7ALAC@:30@/A1=C@B2C16@=;=A=;33A;CB/B7=<A
>3CD3<BAC@D3<7@/C<7D3/C2C5M<3S2=<</<B</7AA/<13I23A
/<=;/:73A23AB@C1BC@323:V03AD/@7/<BA@LAC:B3<B:3>:CA
A=CD3<B 23 ;CB/B7=<A >=<1BC3::3A >@LA3<B/<B 23A B/0:3/CF
1:7<7?C3A D/@7LA  !VLBC23 5L<=BG>7?C3 23A 23CF
>/B73<B3A>=@B3CA3A23;CB/<BA@/>723/@LDL:L:/>@LA3<1323
;CB/B7=</C<7D3/C2C1=2=<23:V3F=<A3
B@/2C7A/<B >/@ :/ AC0AB7BCB7=< 23 :/ 5:G17<3 >/@ :V/1723
/A>/@B7?C33BB3;CB/B7=<1=@@3A>=<2 I:/2L47<7B7=<2VC<3
6L;=5:=07<3 23BG>3 /<59=9 !V6L;=5:=07<33ABC<
D/@7/<B @/@3 23 :V6L;=5:=07<3 ?C7 >3CB @LAC:B3@ A=7B 2VC<3
;CB/B7=<23:/16/O<3SC23:/16/O<3W!V6L;=5:=07<3
/<59=91=<<C3/CAA7A=CA:3<=; =@/B=C0"/</2=
/ LBL 2L1@7B3 >=C@ :/ >@3;7M@3 4=7A 163H C< <=CD3/C <L
2V=@757<3167<=7A33B1/</273<<33<::33AB@3B@=CDL3
3<<2=<LA733<)6/P:/<233B/C8/>=<3B=11/A7=<<3::3;3<B
163H:3A<=7@A/;L@71/7<A3B:3A167<=7A!3AAC83BA
6=;=HG5=B3A3B6LBL@=HG5=B3A>=C@13D/@7/<B23:/16/O<3S
!  :G A> A=<B /AG;>B=;/B7?C3A  < 1/A
2V/AA=17/B7=< /D31 2U/CB@3A 6L;=5:=07<=>/B673A
:V6L;=5:=07<3  /<59=9 >3CB NB@3 @3A>=<A/0:3 23
;/<743AB/B7=<A1:7<7?C3A!V/AA=17/B7=<0/<59=93B0
(1=<AB7BC3C<B/0:3/C1:7<7?C35@/D3(3:=<13@B/7<3ALBC23A
2V/CB@3A /<=;/:73A 16@=;=A=;7?C3A A=<B 7<1@7;7<L3A 2/<A
:3A /AA=17/B7=<A 6L;=5:=07<=>/B673A 1/<13@A 
#=E3: 3B /:  @/>>=@B3<B 23CF 1/A 23 2@L>/<=1GB/7@3A
2LD3:=>>/<B C<3 :3C1L;73 ;GL:=P23 16@=<7?C3 63H 13A
>/B73<BA 23A 2L:LB7=<A 1=;>:MB3 3B >/@B73::3 /C <7D3/C 2C
16@=;=A=;3=<BLBL@3B@=CDL3A
V/CB@3 >/@B  (B@7193@ 3B /:  2/<A :3C@ LBC23
16@=;=A=;7?C323A?C/B@31/A232@L>/<=1GB/7@3A=<B@LDL:L
23A/:BL@/B7=<A/C<7D3/C2C16@=;=A=;3163H23CF;/:/23A
/BB37<BA23:3C1L;73AC55L@/<B/7<A7:/>=AA707:7BL2VC<:73<
16@=;=A=;7?C3 3<B@3 :3A 23CF ;/:/273A %C7A?C3 163H :3A
2@L>/<=1GB/7@3A :3 B/CF 23 27D7A7=< ;7B=B7?C3 3AB L:3DL /C
<7D3/C 23 :/ ;=3::3 =AA3CA3 3B >C7A?C3 :3 @3<=CD3::3;3<B
Région
F=<
B
F=<
F=<
Amorces
#
V))))))V
%
V))))))))))V
V)))))))))V
V)V
Tm °C Position Taille de l’amplification
>0
>0
Tableau 5 : !3A1=C>:3A2V/;=@13ACB7:7ALA>=C@:V/;>:7471/B7=<A>L1747?C323A3F=<A3B2C5M<3S5:=07<3
EXON IVS-1 EXON 2 IVS-2 EXON 3
#%$
Tableau 6 : '3>@LA3<B/B7=<A16L;/B7?C32C5M<3S/7<A7?C3:V3;>:/13;3<B23A/;=@13ACB7:7AL3A

13::C:/7@3/11@C3AB1=@@L:LIC<@7A?C3>:CAL:3DL2V/<=;/:73A
16@=;=A=;7?C3A 7: <V3AB >/A  AC@>@3</<B ?C3 :3 B/CF 23
2LA=@2@3A 16@=;=A=;7?C3A A=7B >:CA L:3DL 163H :3A
2@L>/<=1GB/7@3A
C O N C L U S I O N
#=B@3 LBC23 1=<47@;3 :/ 4@L?C3<13 @3:/B7D3;3<B L:3DL3 23A
6L;=5:=07<=>/B673A 3< ;7:73C 1/@17<=:=57?C3 3B ;=<B@3
:V7;>=@B/<13 23 A=< 2L>7AB/53 I <=B@3 7<AB7BCB /47<
2V/;L:7=@3@:/>@7A33<16/@5323A13A>/B73<BA%/@/7::3C@A
:V6L;=5:=07<3/<59=9<V/8/;/7ALBL2L1@7B3/C>/@/D/<B
3< )C<7A73 :V3F7AB3<13 23 13BB3 /<=;/:73 6L;=5:=07<7?C3
163H  >/B73<BA /BB37<BA 23 BC;3C@A ;/;;/7@3A >=A3@/7B :/
?C3AB7=< 2VC<3 LD3<BC3::3 /AA=17/B7=< AC@ :3 >:/< 5L<7?C3
3<B@313BB36L;=5:=07<3/<59=93B:3>@=13AACABC;=@/:
2CA37<
LA TUNISIE MEDICALE - 2013 ; Vol 91 (n°02)
137
 3@163:7/@/%!=@3B=C1/<!!3)C@2C(/;C3:-
7AB=7@3 </BC@3::3 23 :/ 2@L>/<=1GB=A3 '3DC3 %@/B   
 =AB/<B=>=C:CA  +C::7/;G ) (E7@A9G  '33D3A  /32/ 
!CHH/BB= ! # 6/>:=BG>3A 7< /4@71/<A /<2 E3AB 7<27/<A E7B6
A719:313::/<3;7/=@(127A3/A33<33=5@
 2397:3<B6@=>=:=5G=4SA53<34:=E4@=;,3AB4@71/B=
#=@B6 4@71/ B63 "327B3@@/<3/< /<2 A=CB63@< C@=>3
3;=5:=07<
 "A3227(/@5=C@7!/07/B6.3B/:%@LD/:3<1323A/<=;/:73A
23 :V6L;=5:=07<3 I 307:7 (C2 )C<7A73< '3D>723;7= (/<BL
%C0:
 3<</<7)/;=CH/''=C/0673B/:)63A>31B@C;=403B/
B6/:/AA/3;7/ 7< :53@7/ >=AA70:3 =@757<A =4 B63 ;=:31C:/@
63B3@=53<37BG/<2/B3<B/B7D327/5<=AB71AB@/B35G@/3;/B=:
 3G23 +" !=  6/:74/ $ !G  /::  /BB=C; (
>723;7=:=571/: >@=47:3 =4 63;=5:=07<=>/B673A 7< B63
;/C@7B/<73<>=>C:/B7=<<<3;/B=:
 /E97<A , 7; A (?C7@3A '( 3B /: 1/<13@ 7<1723<13 @/B3
/<2 ;=@B/:7BG @/B3 7< A719:3 13:: 27A3/A3 >/B73<BA /B =E/@2
*<7D3@A7BG6=A>7B/:;3;/B=:
 7/::=)@/=@390/0G"'6/:G/3;=5:=07<=>/B673A
/<2(7<B63=5=<A#=CD'3D@L;/B=:
 (/<5/@3(/<=5="37B3" 3B/:3;=5:=07<$/@/07<D=@G
=/AB/<2E3AB3@<4@71/"32)@=>
 7@1/<(7A:7(CD3<3B/:63;=5:=07<=>/B673A7<B6327AB@71B
=4/<B/:G/BC@93G%327/B@3;/B=:$<1=:=5G
 C16/@=3<(GC9/; (/<16/7AC@7G/ C16/@3<BG>71/:
6/3;=5:=07<  27A3/A3 7< / )6/7 >/B73<B @3AC:B7<5 4@=; /
1=;07</7A=< =4 /:>6/B6/:/AA3;7/  /<2 6/3;=5:=07< =<AB/<B
(>@7<5 E7B6 6/3;=5:=07<  /<59=9 63B3@=HG5=A7BG C@ 
6/3;/B=:
 C16/@=3< ( (7<5A/</< ( (/<16/7AC@7G/  C16/@=3< 
;=:31C:/@ /<2 6/3;/B=:=571/: 16/@/1B3@7A/B7=< =4 1=;>=C<2 60
60 %G@5=A /<2 60 60  /<59=9 7< )6/7 >/B73<BA :7< !/0
/3;/B=:
 (75C3@B + <2@3CF % 7/5<=AB71 07=:=57?C3 23A
6L;=5:=07<=>/B673A >/@ /</:GA3 23A >6L<=BG>3A << 7=: :7<
 (B33<A;/ % 700=<A ' 755A ' 1?C7@32 /:>6/
B6/:/AA3;7/ 7< /AA=17/B7=< E7B6 ;G3:=27A>:/AB71 AG<2@=;3 /<2
=B63@63;/B=:=571;/:75</<173A:==2
 #=E3:: % 3<A3<  /@2<3@)=E 1=;>:3F B@/<A:=1/B7=<A7<
16@=<715@/<C:=1GB71:3C9/3;7/7<D=:D7<516@=;=A=;3A/<2
/B67@216@=;=A=;3C;3<3B
 (B@7193@'!7<93@@=E:3G);0C@G(3;/B=:=571
;/:75</<1G7<A719:313::27A13/A3@3>=@B=44=C@1/A3A/<2@3D73E
=4B63:7B3@/BC@3;63;/B=:
 /::3/A  </5<=AB=>=C:=A  (7<=>=C:=C  3:/97 
"/@5/@7B7A=C@79/A%63<=BG>3/<23<=BG>3@3?C3<1G=4
X)6/:/AA3;7/ /<2 (719:3 3:: 7A3/A3 /@@73@A 7< /:972797
#=@B63@<@33133;=5:=07<
 7557<A)(16</0: (/D=G"'=E3%:/;7<7"/</<2/(
 <=D3: 2=C0:3 63B3@=HG5=CA 0 %C<8/00& <27/
63;=5:=07<=>/B6G:7<7=163;
 )7;0A)'C5:3AA"/::73<<3/GE==2"3<23@A=<
( $:2 " %@3</B/: 7/5<=A7A =4 3;=5:=07<=>/B673A 0G
%G@=A3?C3<17<5"=@3(3<A7B7D3 /<2 '/>72>>@=/16B=3B/:
3<=BG>7<53;=5:=07<
R é f é r e n c e s