CHROMOSOMAL TRANSLOCATION IN A MONGOLOID MALE CHILD
AND HIS NORMAL MOTHER
W I L L Y B E Ç A K * MARIA L U I Z A B E Ç A K * J O Y C E D . ANDRADE * A N T R A N I K M A N I S S A D J I A N * *
The presence of 47 chromosomes in mongoloids, due to the trisomy of
a small acrocentric chromosome in the 21-22 group (Denver system) was
demonstrated by Lejeune et al.
1 1in 1959, and since that time has been
confirmed by numerous authors ( B e ç a k
2) . The production of this trisomy
is explained by a defect in the process by which the homologous
chromo-somes or sister chromatids should dislocate from the opposing poles during
the gametogenesis. Non disjunction which results in the trisomy of 21
chromosome generally occurs in individuals with normal karyotypes and is
influenced by etiological factors associated with maternal age.
The bi-modal distribution of mongolism according to maternal age
shows, in certain cases, the influence of other factors. On the other hand,
the frequency with which, in certain families, there occurs more than one
mongoloid, is higher than expected by coincidence of independent
occur-eences. Also in these cases the maternal age is not a preponderant
etio-logical factor (Penrose et a l .
1 2) .
Investigating cases of mongoloids born of young mothers, Polani et al.
1 3found in one child that the karyotype was abnormal, in spite of the fact that
the child had the normal 46 chromosomes. Instead of one of the large
acrocentrics of 13-15 group they found a larger chromosome which seemed
to be due to the translocation between the absent chromosome with a 21
chromosome. The child, therefore, would be virtually trisomic for the 21
chromosome as in other mongoloids.
Carter et al.
6verified that in the family of a mongoloid with 46
chro-mosomes, the mother, aunt, and maternal grandmother, in spite of apparent
normality, possessed only 45 chromosomes, presenting a translocation
be-tween a number 21 chromosome and a chromosome of 13-15 group. The
simple translocation apparently did not result in phenotypical alterations
in these generations, but made possible the formation of gametes with a
13-15/21 besides the normal 21. The union of a gamete of this type with
a normal one, which carries a 21 chromosome, originates in a zygote with
46 chromosomes, but with the genetic material of 21 in triplicate.
* F r o m the G e n e t i c S e c t i o n o f I n s t i t u t o B u t a n t a n .
Penrose et al.
1 2studied another family in which the grandmother,
mother and daughter were found to have 45 chromosomes. The latter had
given birth to two mongoloid children with 46 chromosomes, verifying in
these karyotypes the existence of translocation 13-15/21.
Fraccaro et al.
9reported a case of a mongoloid male child with 46
chromosomes, but who had only three autosomes in the 21-22 group, verifying
the presence in these cells of an extra metacentric which was interpreted
as an additional 19 or 20, or resulting from a reciprocal translocation
be-tween two 21 chromosomes. The interpretation was complicated by the
presence, in the skin cells of the father of the patient, phenotypically
normal, of what appeared to be an extra 19-chromosome.
Forssman and L e h m a n
8observed, in two phenotypically normal males,
the existence of a translocation 15/21 in one case and 21/22 in the other;
both were parents of mongoloids, bearers of translocations.
Ek et al.
7described the case of a mongoloid male child who had two
sisters and a maternal aunt who were mongoloids. The patient showed 46
chromosomes with apparent reciprocal translocations 15/21.
Breg et al.
5, studying 12 mongoloid patients born of young mothers,
observed trisomy of 21 in 10 cases and translocation 13-15/21 in 2 cases.
The normal mother and brother of one of the mongoloids with 46
chromo-somes were carriers of translocation and showed 45 chromochromo-somes.
Biesele et al.
4also related the case of a mongoloid with 46
chromo-somes. The mother of the child, who was apparently normal, had only
45 chromosomes and presented a translocation 15/21.
In this paper we will describe the case of a male mongoloid child
(Down's syndrome) with a translocation 21/13-15. The mother, who was
phenotypically normal, had 45 chromosomes and the same translocation
21/13-15, which was transmitted to her mongoloid child.
C A S E R E P O R T
A . Z., Jr., w h i t e , m a l e , w a s b o r n F e b r u a r y 13, 1962, o f y o u n g , u n r e l a t e d a n d a p p a r e n t l y n o r m a l p a r e n t s ( m o t h e r 24 y e a r s o f a g e , f a t h e r 3 0 ) . T h i s w a s t h e m o t h e r ' s f i r s t p r e g n a n c y , a n d t h e d e l i v e r y w a s n o r m a l a f t e r 7 h o u r s o f l a b o r . T h e c h i l d w a s s l o w t o c r y a n d b r e a t h e , but s t a r t e d soon a f t e r o r o p h a r y n g e a l c l e a s i n g . B i r t h w e i g h t w a s 2,600 g, l e n g t h 50 c m . T h e r e w a s n o a p a r e n t j a u n d i c e in t h e n e o - n a t a l p e r i o d .
T h e i n f a n t w a s e x a m i n e d on M a y 18, 1962, a t t h r e e m o n t h s o f a g e , a n d s h o w e d r e t a r d a t i o n o f n e u r o - p s y c h o m o t o r d e v e l o p m e n t ( w h e n p l a c e d in a p r o n e p o s i t i o n h e t r i e d b u t w a s u n a b l e t o r a i s e his h e a d ) . H i s w e i g h t a t t h e t i m e o f t h i s e x a m i n a t i o n w a s 5,100 g, l e n g t h 59 c m , c r a n i a l p e r i m e t e r 39 c m , a n d t h o r a c i c p e r i -m e t e r 37 c -m . T h e c h i l d s h o w e d h y p o r e a c t i v i t y d u r i n g t h e e n t i r e e x a -m i n a t i o n a n d t h e skin w a s p a l e a n d d r y . T h e f a c i a l e x p r e s s i o n w a s h y p o m i m i c a l , a l t h o u g h un-c h a r a un-c t e r i s t i un-c . A n e u r o l o g i un-c a l e x a m i n a t i o n r e v e a l e d a s l i g h t g e n e r a l i z e d h y p o t o n i a .
a d i m i n i s h e d h y p o m i m i c a l f a c i a l e x p r e s s i o n . I n a r a d i o l o g i c a l e x a m i n a t i o n t h e d o r s o -l u m b a r c o -l u m n as w e -l -l as t h e h a n d s a n d w r i s t s e x h i b i t e d n o r m a -l b o n e t e x t u r e . T h e p r e s e n c e o f t h r e e n u c l e i o f o s s i f i c a t i o n in t h e w r i s t w a s n o t e d a l o n g w i t h t h e a b s e n c e o f t h e d i s t a l e p i p h y s i s o f r a d i u s . T h e r a d i o l o g i c a l l y e v a l u a t e d b o n e a g e c o r -r e s p o n d e d w i t h t h e c h -r o n o l o g i c a l e v a l u a t i o n .
I n v i e w o f these r e s u l t s a c h r o m o s o m a l s t u d y w a s m a d e t o v e r i f y t h e d i a g n o s t i c h y p o t h e s i s o f m o n g o l i s m . A c y t o g e n e t i c s t u d y o f t h e p a t i e n t a n d his p a r e n t s w a s m a d e w i t h r e s p e c t t o t h e l e u c o c y t e s o f p e r i p h e r a l b l o o d . T h i s w a s d o n e a c c o r d i n g t o t h e B e ç a k t e c h n i q u e 1
.
i n m a l e m o n g o l o i d s . I n g r o u p 6-12-X t h e r e a p p e a r e d 16 c h r o m o s o m e s i n s t e a d o f t h e 15, n o r m a l l y f o u n d in t h e m a l e k a r y o t y p e . T h e c e l l s o f t h e 47 c h r o m o s o m e s o f this c u l t u r e , l i k e t h o s e o f t h e 46 c h r o m o s o m e s , d e m o n s t r a t e d 5 a c r o c e n t r i c s in t h e 13-15 g r o u p and a n e x t r a s u b m e t a c e n t r i c in t h e 6-12-X g r o u p . B e s i d e s this, t h e y a l s o e x h i b i t e d a n a d d i t i o n a l s m a l l a c r o c e n t r i c w h i c h w o u l d be c l a s s i f i e d in t h e 2 1 - 2 2 - Y g r o u p .
T h e m o t h e r ' s c o u n t i n d i c a t e d a s o m a t i c n u m b e r o f 45 c h r o m o s o m e s . I n t h e 23 m e t h a p h a s e s studied, 21 s h o w e d 45 c h r o m o s o m e s , o n e 46 a n d o n e 44. T h e c e l l s w i t h 45 c h r o m o s o m e s , w h e n p a i r e d , a p p a r e n t l y c o n t a i n e d o n l y 5 c h r o m o s o m e s in t h e 13-15 g r o u p i n s t e a d o f 6 f o u n d in n o r m a l i n d i v i d u a l s . T h e 2122 g r o u p l a c k e d a n a u t o -s o m e — o n l y 3 c h r o m o -s o m e -s in thi-s g r o u p a p p e a r e d in t h e k a r y o t y p e i n -s t e a d o f 4 f o u n d in t h e n o r m a l f e m a l e . On t h e o t h e r h a n d , in t h e 612X g r o u p 17 c h r o m o -s o m e -s w e r e c l a -s -s i f i e d i n -s t e a d o f 16 w h i c h a r e c h a r a c t e r i -s t i c o f t h e f e m a l e k a r y o t y p e .
D I S C U S S I O N
The absence, in the mother, of one chromosome of the 13-15 group and
one of the 21-22 group and the absence in the mongoloid patient of one
autosome of the 13-15 group, and the presence in both mother and child
of the extra submetacentric lead to the conclusion that this chromosome
arose by translocation of a small acrocentric 21-22 to a large acrocentric
13-15. The maternal meiotic non-disjunction would produce a gamete with
23 chromosomes containing a. normal 21 chromosom and a 21 translocated.
The fertilization of this ovule by a normal spermatozoid containing a 21
chromosome, resulted in the chromosomal constitution of a mongoloid child
which possessed a pair of 21 autosomes and a translocation 21/13-15 of
maternal origin and therefore a karyotype with 46 chromosomes which in
reality is trisomic for the 21.
The fact that the patient does not possess all the characteristics of
mongolism could be explained by "incomplete trisomy", that is, comprising
all of the 21 chromosome, a segment of which could be lost during
trans-location. The "incomplete trisomy" would be implied in the deficiency of
this same segment in the maternal cells. Notwithstanding, the mother of
the patient is apparently normal.
In this patient two analyzed cells of 47 chromosomes were apparently
tetrasomic for the 21 chromosomes. Besides a translocation 21/13-15 also
encountered in other cells, there is still a small extra acrocentric, considered
as a 21 chromosome. These cells might have originated by a meiotic
"non-disjunction" which, added to meiotic non-disjunction of the same
chromo-some, might have resulted in tetrasomy of the 21. It is possible that the
lack of equilibrium in this chromosomic pair facilitated the occurrence of
new aberrations in the same chromosomic pair, which might explain the
successive alterations observed in relation to the 21 autosome.
It is interesting to note that in all the analyzed cells of the patient
and his father, the Y chromosome appeared significantly larger in relation
to others of the 21-22 group, a phenomenon previously observed by others
(Bender et al.
3, Hungerford
1 0) . It should be noted that in the analyzed
cells of the individuals in one study, the Y chromosome was larger than
the chromosomes of the 19-20 group, corresponding in size to those of pair
18. In some cells the Y chromosome reached the size of pair 17 and even
of pair 16.
S U M M A R Y
The presence of a translocation 21/13-15 is related in 46 chromosomes,
karyotypes of a mongoloid male child (Down's syndrome). The abnormal
chromosome was transmitted by the mother of the patient. The possible
deficiency of translocated chromosome 21 and the possible origin of the
anomaly in the family was discussed and the presence of a markedly large
Y chromosome in the karyotypes of the patient as in those of his father
was also noted.
R E S U M O
É relatada a presença de uma translocação 21-13/15 nos cariótipos com
46 cromossomos de um menino mongolóide (síndrome de Down), sendo o
cromossomo anômalo transmitido pela mãe do paciente. São discutidas a
possível deficiência do cromossomo 21 translocado, e a possivel origem da
anomalia na família. É assinalada a presença de um cromossomo Y
mar-cadamente grande, tanto nos cariótipos do paciente como nos do seu pai.
R E F E R E N C E S
1. B E Ç A K , W . — H u m a n c h r o m o s o m e s in s h o r t t e r m c u l t u r e s f r o m p e r i p h e r a l b l o o d l e u c o c y t e s . R e v . B r a s . B i o l . , 21:281286, 1961. 2. B E Ç A K , W . — D e s e n v o l v i -m e n t o e a p l i c a ç õ e s d a c i t o g e n é t i c a h u -m a n a na p a t o l o g i a . R e v . B r a s . C i r u r g . , 44: 298-310, 1962. 3. B E N D E R , M . A . and G O O C H , P . C. — A n u n u s u a l l y l o n g h u m a n Y c h r o m o s o m e . L a n c e t 2:463-464, 1961. 4. B I E S E L E , J. J.; S C H M I D , W ; . L E E , C. H . a n d S M I T H , P . M . — T r a n s l o c a t i o n b e t w e e n a c r o c e n t r i c c h r o m o s o m e s in a 46 c h r o m o s o m e m o n g o l o i d and his 45 c h r o m o s o m e m o t h e r . A n n . J. H u m a n . Gen., 1 4 : 125-134, 1962. 5. B R E G , W . R . ; M I L L E R , O . J.; S C H M I C K E L , R . D . — C h r o m o s o m a l t r a n s l o c a t i o n s in p a t i e n t s w i t h m o n g o l i s m and in t h e i r n o r m a l r e l a t i v e s . N e w E n g l . J. M e d . , 266:845-852, 1962. 6. C A R T E R , C. O . ; H A M E R T O N , J. L . ; P O L A N I , P . C ; G U N A L P , A . ; W E L L E R , S. D . U . — C h r o m o s o m e t r a n s l o c a t i o n as a cause o f f a m i l i a l m o n g o l i s m . L a n c e t 2:678680, 1960. 7. E.K. J. D . ; F A L K , V . ; B E R G M A N , S.; R E I -T A L U , J. — A m a l e m o n g o l o i d w i t h 46 c h r o m o s o m e s . L a n c e t 2:526-527, 1961. 8. F O R S S M A N , H . ; L E H M A N N , O . — T r a n s l o c a t i o n c a r r y i n g p h e n o t y p i c a l l y n o r m a l m a l e s a n d t h e D o w n s y n d r o m e . L a n c e t 1:1286, 1961. 9. F R A C C A R O , M . ; K A I J S E R , K . ; L I N D S T E N , J. — C h r o m o s o m a l a n o r m a l i t i e s in f a t h e r and m o n g o l c h i l d . L a n c e t 1:724-727, 1960. 10. H U N G E R F O R D , D . A . — O b s e r v a t i o n s on t h e m o r p h o l o g y a n d b e h a v i o r o f n o r m a l c h r o m o s o m e s ( i n p r e s s ) . 11. L E J E U N E , J.; G A U T I E R , M . ; T U R P I N , R . — L e s c h r o m o s o m e s h u m a i n e s en c u l t u r e d e tissues. C o m p t . r e n d . A c a d . Sc. ( P a r i s ) 248:602-603, 1959. 12. P E N R O S E , L . S.; E L L I S , J. R . ; D E L H A N I Y , J. D . — C h r o m o s o m a l t r a n s l o c a t i o n in m o n g o l i s m and in n o r m a l r e l a t i v e s . L a n c e t 2:409-410, 1960. 13. P O L A N I , P . E . ; B R I G G S , J. H . ; F O R D , C. E . ; C L A R K E , C. M . — A m o n g o l g i r l w i t h 46 c h r o m o s o m e s . L a n c e t 1:721-724, 1960.
