American Journal of Medical Genetics 35595-599 (1990)

GENE O F TYPE I1 AUTOSOMAL DOMINANT RETTNITIS PIGMENTOSA MAPS ON THE LONG ARM OF CHROMOSOME 3

Olsson, Ch. Samanns, J . J i m e n e z , J. P o n g r a t z , A . Chand, Wattv, S . A . S e u c h t e r , M . D e n t o n , and A. G a l Departnieii t q t t ' a t h n l wn-, P i 1 nc-e o f Iz'a Les H o s D i t-a L . Kandwi c k , Sl-dnel' NSlv 2 0 3 1 A u s t r a l i a ( J . E . O . , J . J . , X . C . , Y.D.1 : I n s t i t i i t f i i r FIiiiiianqeuet i k ( ( ' . s .. J . I J . , .A.K. , A . G . ) aiid I i i s t i t u t f u r Yedizinische S t a t i s t i k (S.X.S) , Uni!-ersit\- f j t H ( J i i i i , B o i i i i , E-Rc;

J.E. A.

AR STRACT

K e 1 7 words: Autosoinal Dominant Keti-

n i t i s Piunientosa L i n k a q e a n a l y s j s h a s been oer formed on a l a r g e A u s t r a l i a n f a m j l v s e g r e q a t i n q for t h e aiitosomal domj n a n t f o r m of r e t i n i t i s p i q m e n t o s a ( A D R P ) . The m a j o r i t y ot p a t i e n t s had n o s u b j e c t i v e symptoms of n i g h t b l i n d n e s s !inti 1 t h e i r second d e c a d e a n d qood v i s u a l a c u i t v u n t i l l a t e i n l i f e . The d i s e a s e 1 1 1 t h i s f a m i l y h a s b e e n c l a s s i f i e d a s Tvpe I T ADRP a c c o r d i n q t o t h e s i i b d i v i s i oris prov i d e d bv b o t h Massof and F i n k e l s t e i n and Fishman a n d col leaques. Linkage :0.08 a t Z m a x :4.78) i s here d e m o n s t r a t e d between t h e d i sease l o c u s a n d D3S47 ( a m a r k e r loc u s on t h e lonq arm o t chromosome 3 1 , which showed i n a n e a r l i e r s t u d y v e r y close L i n k a q e w i t h o u t recombination t o t h e disease l o c u s i n an I r i s h pediqree with a c l i n i c a l l y more s e v e r e a n d e a r l y o n s e t (Type I ) ADKP.

Received for publication October 20, 1989; revision received December 19, 1989.

Address f o r a l l c o r r e s p o n d e n c e : Andreas G a l , PI. D . , P h . D . I n s t i t u t f u r Huinaiig en e t i k \C i 1he l m s t r a s s e 3 1 D - 5 3 Boiin 1 F e d e r a 1 R e pu b 1i k Q f tier m any 0 1990 Wiley-Liss, Inc.

C lir omoseine 3 L i n k a(xe an a 1\-s1 s

D3S47 i;ei?et L C !!anDinn

INT R ODL'C T I ON K c t i i i i tis Dicrtiientosa ( R P ) is t h e inost coinmon h e r e d i t n r \ deaeiier a t i i ' e d i s e d s e of t h e r e t i n a 111 inan which f r e q u e i i t l \ l e a d s t o se\-ere x-isiidl haiidic;ap or b l i n d n e s s i n e a r l \ - adulthood [Bctuclhniaii and F i s h illail, 1'9831 K P is b o t h g e i i e t i s a l i v aiid c l i n i c a l l y h e t e r o g e n e o u s [for rex'iek s e e H e c k e n l i x e l y , 1 9 8 8 1 . As f o r t h e p a t t e r n ot i n h e r i t a n c e , a u t o s o m a l doiitinaiit diid r e c e s s ] \-e . aiid S - l i n k e d torms a r e k n o h i i . I n \-let< ot t h e q r e a t c l i i i ~ c a l X - a r i a b i l i t \ nf RP, f u r t h e r a e n e t i c lieteroaei i e i t l - \ < i t t i i n e a c h of t h e t r a i t s i s

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Olsson et al.

vex-)- l i k e l l - . I n d e e d , l i n k a g e stud i e s a s E e l 1 a s d e l e t i o n mapping Iia\-e s t r c m g 1 ) - s u g g e s t e d t h a t a t l e a s t t w o d i f f e r e n t l o c i t o r 1l i n k e d KP e x i s t [Chen e t a l . , 1 9 8 9 ; F r a n c k e e t al., 1985; t i i r t h e t a l . , 1988). In a s i n g l e larae pedigree s e g r e q a t i n q f o r a s e \ - e r e for111 of aiit.c)saiiial d o n i i n a n t r e t j l l i t j s p i c [ - mentosa (ADRE') , 3 c l < i l l . jam a n d c d 1e a q u e s [ I c)f(9 1 foltlld x-eri- c l o s e 1i n k a g e f i i t Iiou t r e com b i H a t i o n (Onlax : 0 . 0 0 Z m a s :14.7) b e t u e e n the d i s e a s e locus ( R P i ) and t h e DNA p r o b e l o c u s DljS-1'7. The l a t t e r i s c h a r a c t e r i z e d by a f r e q u e n t R F I I P d e t e c t e d bg- p r o b e CRI--r:'17 and maps on t h e l o n g arim of chrnmosnrae 3 [Kidd e t a l . , 1989 J .iccordinql J-, t h e l o c u s c a u s i n g RP i n t h a t fainif!h a s been assigned t 3q. Here ~e r e p o r t t h e r e s u 1 . t ~of a l i i i k a q e a n a l y s i s r;ith C R I . C l ' / 1 1 1 a l a r g e Australian famill- seareaat i n q f o r a m i l d e r form o f autc)so,nial dominant R P . A 1 s c ) i i ? t h i s fanii 1 \ - , l i n k a g e h a s been found b e t l i e e n tlie d i s e a s e locus a n d D 3 S 4 7 .

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80

f eiic)us b l o o d has c o l l e c t e d f r c w 51 i i i c l i \ - i d u a l s t o r e s t r a c t i o n clt D h h . ?he d i a e s t i o n of DNA and S o u t h e r n b l o t hybridization here a s p r e \ - i m s11 d e s c r i bed iD e n t 011 e t al., 1 9 8 4 1 . Probe C R I - C I S / h a s 131-9vicfed 1?\ ('01l a h o i a t i \-e R e s e a r c h , riic. Hedt trd ( 1 SL\) T l i p c-orrespoildinn r)KA ~ O ~ Y I (D3S-17) S l i d s been maDped on chromnsoine 3 I k i d d et a l , , 1 ~ ) 8 q.] T h e humaii i n s e r t of I

IS 'li a b n i i t -40 k i l o b a s e s ( k b ) . A r t e r e i t h e r hlfsr>I ~r T a u 1 d i gestion aenomis D N A , t h e p r m e d e t e c t s t L O po 1vmo r a h 1 c t r a anie 11 t s (Al/A2, B1/B2 and L L / C ~ , r ) l / ~ 2 . r e s p e c t i \ el\ ) a n d sel-era1 i n \ a r i a b l e cmes. he u s e d a ca. 1 4 k b E c o R l fraqrneiit ot the e n t i r e CRI-Cl7 liisei-t a s tlie ui(>1ec'iliar o r o b e h h i c h allo1,ed t h e detectir1ii r)f a l l e l e sist-erns - i J /A2 and C l / C 2 . S i n c e in this f a m i l l a l l e l e s A and C cos e q r e q a t e and t h e r e is n~ e v i d e n r e €c?r contple t e 1i i i k a a e d 1 s e a u i 1112r i iiui betr,eeii t h ~ i n , cc>mbined t h e YspI a n d TaqI p r o b e p l i e n o t \ w e s i n t o

C R l ('17

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Gene of type II autosomal dominant retinitis pigmentosa maps on the long arm of chromosome 3.

Linkage analysis has been performed on a large Australian family segregating for the autosomal dominant form of retinitis pigmentosa (ADRP). The major...
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