Hum Genet (1987) 75 : 93-94

© Springer-Verlag 1987

Prenatal diagnosis of a 46,XX,inv (12) pat/47,XX,i (Xq) ,inv (12) pat

Maria Varela, Nancy Wang, and Mabel Cerrillo

The Human Genetics Program, The Hayward Genetics Center, Tulane University, School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA

Summary. A 46,XX,inv(12)pat/47,XX,i(Xq),inv(12)pat was diagnosed prenatally in a 36-year-old woman whose husband was a known carrier of a pericentric inversion of chromosome 12. The diagnosis was confirmed in fetal tissue. Terminal bromodeoxyuridine (BrdU) labell ingdemonstrated that in the line with 46 chromosomes one X was late replicating, while one X and the i(Xq) were late replicating in 100% of the cells with 47 chromosomes. We present the first case of this type of sex chromosome mosaicism. Genetic counseling presented difficulties since it was not possible to predict the fetal pheno- type.

Introduction

Among the structural rearrangements of the X chromosome, the most frequent type is the isochromosome of the long arm (Davidenkova et al. 1978). Approximately 60% of the iso Xqs reported, were observed in mosaic form (Schmid et al. 1974; Palmer et al. 1976; Fujita et al. 1977), of which the most com- mon type is 45,X/46,X,i(Xq). In this brief report we present the first case of a mosaic, with the karyotype 46,XX,inv(12) pat/47,XX,i(Xq)inv(12)pat ascertained in amniotic fluid cells and confirmed in skin fibroblasts from the fetus. Problems re- garding genetic counseling will be presented.

Fig. 1. Karyotype of the 47,XX,i(Xq)inv(12)(p13q22)pat cell line found in the fetus

Offprint requests to: M. Varela

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ture studies. Permission for complete autopsy was not granted by the parents.

Fig.2. Terminal BrdU labelling to demonstrate that the isochromo- some (dark arrow) and one normal X (open arrow) were late replicat- ing in the line with 47 chromosomes

Case report

A 36-year-old Gravida 3, para 2, abortion 0, requested pre- natal cytogenetic study both because of age and because her husband was a known carrier of a familial pericentric inver- sion of chromosome 12 [46,XY,inv(12)(p13q22)]. His brother and two nephews were carriers of the inversion while neither of his daughters carried it. Amniocentesis was performed at 15 weeks gestation. Ninety-two cells were analyzed with GTW from four different culture flasks. Fifty-four percent of the cells revealed a 46,XX,inv(12)pat karyotype while the other 46% were 47,XX,i(Xq)inv(12)pat. Amniocentesis was re- peated at 18 weeks. One hundred cells from two different flasks were analyzed of which 62% showed the 47,XX,i(Xq) line (Fig. l ) . R-banding using pulse bromodeoxyuridine (BrdU) was used to identify the replication patterns of the X chromosomes. In 100% of the cells analyzed from the 47 line the i(Xq) and one of the normal Xs were late replicating (Fig.2). C-banding showed that the isochromosome had a single centromere.

After extensive genetic couseling the couple elected termi- nation at 20 weeks gestation. Skin cultures from the apparent- ly normal fetus were established in two different flasks. Fifty cells were studied of which 60% presented the 47,XX,iso(Xq) inv(12) line, confirming the diagnosis of the mosaic. A fibro- blast cell line was established from the amniotic cells for fu-

Discussion

Although prenatal cytogenetic diagnosis can usually provide parents with information as to the phenotype of the fetus, there are problem cases such as the one presented in this com- munication. Malformations related to the inversion(12) were not expected since it was identical to the one present in the father and other members of his family. The counselling prob- lems was related to the sex chromosome aberration. In cases in which the cytogenetic diagnosis reveals a 46,XX/46,X,i(Xq), 45,X/46,X,i(Xq), or 46,X,i(Xq), the phenotype is known to be similar to that of Turner syndrome due to monosomy of an X or the loss of the short arm of one X in part or all of the so- matic cells. Turner syndrome was not expected since mono- somy of Xp was not observed in any cell. In the present case, disomy for Xp in all cells and tetrasomy for Xq in 60% of the cells was found. Although the isochromosome was late repli- cating in all the cells, the damage to the fetus during the early embryonic stage, due to the presence of four long arms of the X could not be completely ruled out. It is possible that had there been any problems in this fetus, developmental delay would have been the most likely. Help was not encountered in the literature since similar cases have not been reported.

Other colleagues were consulted but none would commit themselves due to lack of previous experience. In essence, the phenotype of the fetus could not be accurately predicted.

Acknowledgements. We thank Mrs. Viola Blackman for her technical assistance and Ms. Kim Negrotto for typing the manuscript.

References

Devidenkova ET, Verlinskaja DK, Mashkova MV (1978) Structural aberrations of the X chromosome in man. Hum Genet 41:269- 279

Fujita H, Tanigawa T, Yoshida Y, Okada Y (1977) Cytological find- ings of 10 cases with i(Xq) and one with dic(X)(qter~---cen~ p22: : pll~---qter). Hum Genet 39 : 147-155

Palmer CG, Reichmann A (1976) Chromosomal and clinical findings in 110 females with Turner syndrome. Hum Genet 35 : 35-49

Schmid W, Naef F, Murset G, Prader A (1974) Cytogenetic findings in 89 cases of Turner' syndrome with abnormal karyotype. Human- genetik 24: 93-104

Received June 30, 1986 / Revised August 18, 1986