An unbalanced 4q/21q translocation identified by the R but not by the G and Q chromosome banding techniques


DUTRILLAUX B., JONASSON J., KERSTIN Laurén, LEJEUNE J., LINDSTEN J., PETERSEN G.B., SALDAÑA-GARCIA P. (1973). - An unbalanced 4q/21q translocation identified by the R but not by the G and Q chromosome banding techniques. Ann. Génét., 16, n° 1, 11-16.

Résumé :

Chez une femme de 54 ans, débile mentale avec microphtalmie, on observe une apparente monosomie 21 (45,XX, -21). L'analyse des bandes Q et G (Quinacrine et Giemsa) ne révèle pas d'autre anomalie. Seule l'analyse des bandes R montre que la partie distale du 21 manquant est portée par le bras long du 4. La patiente est donc monosomique pour la region juxtacentromerique du 21 et, peut-être, pour la region télomérique du bras long du 4.


Only a few subjects have been reported to have congenital autosomal monosomy. Most of them have been mosaics with one 45,-G cell line and one or two more cell lines with a normal karyotype and/or a structural chromosome abnormality involving a G chromosome (reviews in Greenwood and Sommer 1971 and Weber et al. 1971) (Emberger et al. 1970). To our knowledge only four congenital, apparently non-mosaic cases with presumptive G monosomy have been published (Thorburn and Johnson 1966, Al-Aish et al. 1967, Hall et al. 1967 and Gripenberg et al. 1972). In one of these cases the karyotype was interpreted as 45,X,-21 by quinacrine fluorescence analysis (Gripenberg et al. 1972). In the present paper we report on a 54 years old mentally retarded woman who originally was considered to have a presumptive monosomy 21 on the basis of an analysis of the direct Giemsa (G) and quinacrine (Q) chromosome banding patterns. However, later studies using the reversed Giemsa (R) banding technique demonstrated an unbalanced 4q/21 q translocation.


Case report

The patient, a female born in 1919, was an only child, and the mother had probably not had any spontaneous abortions. Nothing is known about the pregnancy and the delivery or about the birth weight of the patient. The mother was German and the father Swedish, and thus there was no consanguinity. Her father was 39 and her mother 32 years old at her birth. The father died when the patient was young. The mother died in 1967, and since then the patient has been taken care of in an institution for the mentally retarded. There is almost no information available about the patient before 1967, but she had apparently been healthy and was not unusually susceptible to infections. No other cases of mental retardation or malformations are known in the family.

At the last examination, at 54 years of age, the following observations were made (fig. 1). Short stature with body height 140 cm, weight 43.5 kg and head circumference 54.5 cm. She was blind and had congenital microphtalmia. There were no other obvious external malformations, but her hands and feet were rather slender. The secondary sex characteristics were normal for the age, but it was not possible to obtain information regarding menstruation and age at climacterium.

She walked with raised arms as blind persons do, and needed some support. Her reflexes were rather strong, Babinski's sign could not be elicited. Twice before and four times after 1967 she had had fractures which included the collum of the femur, the fingers and the ankles. X-ray examination revealed generalised osteopenia. The joints were normal. Her hearing was also apparently normal. Physical examination gave no evidence of a heart malformation. The palate was normal, but there was a moderate overcrowding of the incisors in both jaws.

The patient's native language was German, and she spoke German as well as Swedish fluently. She was well orientated in time and space and had a very goad memory. Some help with her personal care was needed. She was even tempered and good natured. Only a very rough estimate of the intelligence quotient could be made because of her blindness. The intelligence profile was apparently very uneven. The memory was rather good and the vocabulary (in Swedish) correspond to an IQ of 65. The ability to understand and draw conclusions was considerably reduced, the IQ being about 50.

Fig. 1. - The patient at 54 years of age: a) full picture; b) face


Cytogenetic analysis.

The patient was sex chromatin positive in cells from buccal mucosa smears. A 45,XX,-G karyotype was consistently found in repeated lymphocyte cultures and one fibroblast culture of a skin biopsy. One hundred cells were analysed from each tissue.

Analysis of the banding pattern of the chromosomes after quinacrine (Caspersson et al., 1971) and Giemsa (Summer et al. 1971 ) staining showed only one chromosome 21, but an otherwise normal female karyotype (fig. 2). However, evidence in favour of an unbalanced 4q/21q translocation was obtained by the reversed Giemsa banding technique (Dutrillaux and Lejeune, 1971). As seen from figure 3 the normal chromosome 21 has a prominent dark band at the end of the long arm. A similar band can be seen at the end of the long arm of one chromosome number 4, which normally has a tiny dark band in this region. No measurable size differences were found between the two chromosomes number 4. There were no other obvious abnormalities noted.


Analysis of genetic markers.

A number of genetic markers were analysed at different laboratories (see Ackowledgments), and the following results were obtained. Blood groups: B; MN; ss; P1; R1 R2,; K+ k+; FYa+ FYb+; JKa- Jkb+; Lua- Lub+; Lea- Leb-; Coa + . Serum protein groups: Hp 2-2; Tf C; C'3 2; Pi M; Gc 2-1; Gm (+ 1,-2,+ 4,+5,+ 10,+14,+17); Inv ( - 1). Red cell enzymes:AcP BA; PDG A; PGM1 2-1; PGM3, 2-1; AK 2-1 ; ADA 1; Pep A,B,C,D 1 ; GPT 2-1. HL-A, typing showed the presence of four antigens (1, 2, LNDx, SL-ET). Thus, the patient was clearly heterozygous at the following 12 loci: MN; Rh; Kell; Duffy; Gc; acid phosphatase, phosphoglucomutase 1 and 3, adenylate kinase, glutamate-pyruvate transaminase, HL-A and most likely Gm.


Dermatoglyphic analysis.

The finger print patterns (fig. 4), six whorls and four ulnar loops, are not typical of Down's syndrome; in mongols whorls are reduced in number but ulnar loops show a high frequency.

The total ridge count (212) is well above the average for English female mongols (124) and even higher than that found in Turner's syndrome (169); mongols tend to have, on the average, a. slightly lower total ridge count than the general, population (O 127, S.D. 52).

On the palms, the presence of a peripheral loop III on the right side, and the distal position of the axial triradius (t') on both sides, are dermatoglyphic features which are not against the diagnosis of mongolism. Pattern intensity, however, is low; the mean number of loops per palm is here 1.0 against 1,88 in English mongols (males and females combined), and the absence of pattern in the hypothenar area is not characteristic of 21 trisomy; in mongols a peripheral loop H occurs with a frequency of 66.5 per cent.

On the soles, dermatoglyphic features characteristic of Down's syndrome such as an open field an the hallucal area of the sole or a distal loop on area IV are not present in the patient's soles. She has, however, a distal loop I an the hallucal area of bath soles but the quality of the prints did not permit measurement of the size of the loop.

A small distal loop I containing 20 or less ridges is about three times as common in mongols as it is in controls while large loops, ridge count over 20, have in female mongols a frequency of 15.5 per cent on the left : and right soles but of 45.5 and 47.3 per cent, respectively, in English female controls.

The zygodactylous z triradius which seems to be present on the left sole is rare in mongolism.

Finally, the anti-mongol tendency shown by the patient's dermatoglyphic configurations was ascertained by calculating the probability of her being a mongol (Penrose and Smith 1966, Holt 1968 and Penrose and. Loesch 1971). This probability was found to be between 1 /30 to 1 /750 (the discriminant value x = 5050).

Fig. 2 - Quinacrine (a) and Giemsa (b) stained karyotypes showing a presumptive 45, XX, - 21 chromosome constitution wihout evidence of a translocation.



It has generally been assumed that congenital autosomal monosomy in man would be very rare, since it would very likely be too genetically unbalanced for survival. In fact, very few such eases have been reported, and most of them have been mosaics involving one chromosome in the G group. Even among spontaneous abortuses autosomal monosomy seems to be very rare indeed (Larsson et al. 1970, Carr 1971). Only the case of Gripentberg et al. (1972) has to our knowledge been analysed with regard to the chromosome banding pattern. This case was reported to have a presumptive monosomy 21.

Originally the present patient was also considered to have monosomy 21. However, several observations did not seem to favour this interpretation. Firstly, the patients somatic defects were relatively limited, as in the case of Gripenberg et al. (1972). This could of course be explained by a non-detected mosaicism, a possibility which seems unlikely but can not be completely ruled out. Secondly, if monosomy 21 is not associated with more severe anomalies, it should have been recognized among the offspring of D/21 and 21/22 translocation carriers. To our knowledge no such case has been described, and it is highly unlikely that it has been overlooked. Thus, even if the present patient originally appeared to have a pure monosomy 21, a translocation involving one chromosome 21 could not be totally excluded, and in fact an unbalanced 4q/21 q translocation was later demonstrated.

The translocation could only be identified by an analysis of the R-banding but not by the G- and Q banding patterns. This is due the fact tree R technique gives a particular clear staining of those chromosome tips which are weakly stained with the other methods. In the present case the distal end of chromosome 21, which has a prominent dark R-band, had apparently been translocated on to the distal end of chromosome 4. This could be demonstrated only because the R-band at the tip of the normal chromosome 4 is very much smaller than the one on chromosome 21. Since the fluorescent band on the middle of the long arm on chromosome 21 X21 q21) could not be seen on either chromosomes 4, the break on chromosome 21 has probably occurred in the proximal part of band 21q22 (nomenclature of the Paris Conference 1971). The exact location of the break point on the long arm of chromosome 4 could not be evaluated. Since both chromosomes 4 were of the sage size the break point ought to be located in or distal to band 4q33.

Fig. 3. - Reversed Giemsa stained karyotype showing a prominent dark band at the end of the long arm of one chromosome number 4. This band is similar in size to that seen on the long arm of the only chromosome 21 present.

Fig. 4 - Dermatoglyphic pattern of the patient's hand (a) and feet (b).



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