SIR, -Your editorial (1) on the mongol chromosome and others drew
attention to translocations. The practical and theoretical interest of these
The first recorded example was the 22/13 translocation (2), but 6
others are now known. Some involve the mongol chromosome: 21/13 or /14, or /15
(3), 21/22 (4), or 22/22, 21/21 (5), 21/15 (4, 6). You stated (1) that these
explain the occurrence of " exceptional 46-chromosome mongols ", and of the
rare cases where 2 sibs are affected (4, 6). Other translocations have been
reported : 14/15 (7), 22/13 (8), a and a possible 21/Y (9).
Thus translocations appear to play a well-defined role in pathology.
It is noteworthy that all the types so far recorded involve acrocentric
chromosomes. This kind of rearrangement is, of course, most easily recognised,
for reciprocal interchanges between metacentric elements of comparable size
would be difficult to assess, and would merely lead to wrong classification
when establishing the karyotype. Thus, the observations may be biased. But the
presence of satellites in nos. 13, 14, and 21 could play a role in the
translocation mechanism, and in determining the probability of its
Furthermore, the so-called " centric fusion " implies a deletion of
the chromosomal segments attached to the eliminated centromere. Hence the more
acrocentric the elements, the smaller will be the chromosomal loss. In view of
the possible lethal effect of big autosomal deletions (none has been observed
as yet) this prevalence of translocations between acrocentric chromosomes could
well result from natural selection.
The practical interest of translocations is not restricted to genetic
counselling in familial mongolism. The 14/15 type was found in an individual
also exhibiting the XXY Klinefelter syndrome (7). A mother carrying a balanced
22/13 translocation gave birth to a classical mongol with 47 normal chromosomes
and 3 no. 21 chromosomes, and without the maternal translocation (8). The fact
that translocations seem to increase the probability of non-disjunction in
other chromosomes invests the discovery of a translocation in an apparently
healthy individual with eugenic significance. The diagnostic interest of
translocations is mainly dependent on their phenotypic consequences. For
example, all the healthy carriers of the different 21/13 varieties with a
balanced 45-chromosome genotype have been reported to be normal. The "
exceptional 46-chromosome mongols " are phenotypically indistinguishable from
A possible conclusion would be that the loss of satellites does not
have harmful effects, because of the low genic content of these segments.
By contrast the two varieties of the 22/13 type seem harmful. In the
first case (multiple vertebral dysgenesis) (7) vertébral deformities and
mental and physical retardation were observed. The second exemple (8), observed
in a mother and in 4 of her children, determined various degrees of speech
defect and mental retardation, ranging from very severe in the children to
normality in the mother.
These intrafamilial variations between carriers of the same variety
demonstrate the influence of the rest of the genotype. But the interfamilial
variation between different. varieties of the same type could be attributed to
the extent of change in each variety-i.e., the eliminated fragments could
If the effect of position is ignored, at any rate in a preliminary
survey, a sample of, say, 20 varieties of the 22/13 type could yield much
information about the genic content of the eliminated fragment. For example, if
it was observed that 2 characters, which are sometimes independent, are always
accompanied by a 3rd, when both are present together, a threepoint linkage map
would be obtained; and its spatial relationship to the centromeres could be
established. To determine whether the eliminated fragment belonged to no. 22 or
to no. 13 would depend upon comparisons between types 22/13 and 22/15.
The method is limited by the shortness of the analysable fragment.
This is due to the harmful effect of autosomal deletions.
Some types in which the deleted fragments are genetically quite
inactive could very well be transmitted unknowingly in our species. Thus, a
possible polymorphism of the karyotype among apparently normal people, even
though very rare (7), cannot be ruled out.
This discussion of cytogenetic mapping of chromosome segments would
probably have been considered unrealistic a year ago. But with the worldwide
expansion of research in cytogenetics, the requisite sample of many varieties
of the same type is likely to be obtainable fairly soon.
It would be beneficial if authors working in this field gave as much
attention to precise phenotypic description as to accurate chromosome
1. Lancet, 1960, ii, 1068.
2. Turpin, R., Lejeune, J., Lafourcade, J., Gautier, M. C.R. Acad.
Sci., Paris, 1959, 248., 3636.
3. Polani, P. E., Briggs, J. H., Ford, C. E., Clarke, C. M., Berg, J.
M. Lancet, 1960, i, 721.
4. Penrose, L. S., Ellis, ]. R., Delhanty, J. D. A. ibid. 1960, ii,
5. Fraccaro, M., Kaijser, K., Lindsten, J. ibid. 1960, i, 724.
6. Carter, C. O., Harnerton, J. L., Polani, P. E., Gunalp, A., Weller,
S. D. V. ibid. 1960, ii, 678.
7. Lejeune, J., Turpin, R., Decourt, J. C.R. Acad. Sci., Paris, 1960,
8. Moorhead, P. S., Mellman, W. J., Wenar, C. Amer. J. Genet. (in the
9. Turpin, R., Lejeune, J., Gautier, M. Conference on Congenital
Malformations. London. July 18-22. 1960.