Dec 14, 1992 - Ernest B. Hook .... effect is blocked by H-Y antiserum (Mtiller and Urban ... hCG ", t . ~". """ 5. 2.5. 1.25 .625. C. Antigen Dilution (~g/ml). Fig. 1.
Hum Genet (1993) 91:514-518
human--
genetics
9 Springer-Verlag 1993
Letters to the editors Choroid plexus cysts diagnosed prenatally as an independent risk factor for cytogenetic abnormality Ernest B. Hook School of Public Health, University of California, Berkeley, CA 94720, USA Received: 8 October 1992
Zerres et al. (1992) state on the basis of six cases reported in the literature with trisomy 21 and choroid plexus cysts that "prenatally diagnosed choroid plexus cysts should in all cases be regarded as an indication for prenatal chromosomal diagnosis because additional abnormalities in trisomy 21 are sometimes absent in the second trimester" (emphasis added). But the fact that some reported trisomy 21 cases have choroid plexus cysts but no other ultrasonically detectable abnormalities is of uncertain relevance to clinical practice. One needs pertinent data on controls. The authors' reported data indicate only that the presence of choroid plexus cyst is at best an equivocal finding. They report that of 823 fetuses exhibiting developmental abnormalities defined as "growth retardation/malformation," 168 (20.4%) had a cytogenetic disorder. In the 25 of the 823 in which choroid plexus cysts were diagnosed, they report 5 (20%) in which there was a cytogenetic disorder. Thus, one may calculate that in those without choroid plexus cyst but with growth retardation/malformation, the proportion with cytogenetic abnormally actually is 163/798 = 20.4%, or actually slightly higher than in those with such cysts. This result casts significant doubt on the clinical utility of observation of the cyst, or the authors' conclusion cited above. Their data do tend, however, to support the inference that the presence of "abnormalities" in addition to choroid plexus cyst in those with "growth retardation," is suggestive of a cytogenetic defect, but primarily trisomy 18. Of the 11 with such additional abnormalities 5 (45%) had a cytogenetic defect, (4 with 47 + 18, one with 47 + 21), whereas one may calculate from the authors' data that none (0/14) of those without other defects had normal karyotype. This difference has a two-tailed probability of about 0.002, and is thus nominally significant. Unfortunately, interpretation of even these data from a clinical perspective requires knowledge of the level of intensity with which they scanned the ultrasound after finding choroid plexus cysts, and when in gestation malformation was noted. The likelihood of recognition of fetal malfor-
mation in ultrasound varies markedly with the size of the lesion, knowledge of the region likely to be affected, and the age of the fetus. Some abnormalities may be very difficult to diagnose and only recognized retrospectively on ultrasound after knowledge of presence of the malformation, or only at late stages of pregnancy, when, in many jurisdictions, a patient may no longer have the option to terminate pregnancy. At best the results suggest that in a conceptus with choroid plexus cyst and growth retardation, the presence of another malformation on ultrasound may increase the likelihood that a karyotypic abnormality is present. The precise nature of this increase in likelihood cannot be evaluated from the data.
Reference Zerres K, Schuler H, Gembruch U, Bald R, Hansmann M, Schwanitz G (1992) Chromosomal findings in fetuses with prenatally diagnosed cysts of the choroid plexus. Hum Genet 89:301-304
Hereditary hydronephrosis and the short arm of chromosome 6 J. P. Fryns 1, A. Kleczkowska l, P. M o e r m a n 2, K. Vandenberghe 3 1 Centre for Human Genetics, University Hospital, Herestraat 49, B-3000 Leuven, Belgium 2Department of Pathology, University Hospital, Herestraat 49, B-3000 Leuven, Belgium 3 Department of Gynaecology and Obstetrics, University Hospital, Herestraat 49, B-3000 Leuven, Belgium Received: 27 August 1992
We read with interest the paper by Izquierdo et al. (1992). The authors performed linkage analysis in 5 families with hereditary bilateral pelvi-ureteric junction (PUJ) obstruction, using the major histocompatibility complex locus as a test marker, and found data supporting the assignment of one of the loci for hereditary hydronephrosis to chromosome 6p. Recently, we performed prenatal diagnosis on a 26-yearold primigravida after the detection of oligohydramnios Correspondence to: J. P. Fryns
515 with bilateral multicystic renal dysplasia on routine echographic examination at 20 weeks gestation. Chromosomal analysis of the amniotic fluid cell cultures revealed a 46,XX,t(6;19)(p23.1 ;q13.4) de novo karyotype in all 20 analyzed cells. Prostaglandin induction was performed at 23 weeks after ultrasonographic confirmation of the extreme oligohydramnios. Autopsy confirmed the presence of bilateral multicystic renal dysplasia, more pronounced on the right side, with bilateral PUJ obstruction resulting in massive hydronephrosis. Except for external morphological stigmata and severe lung hypoplasia secondary to the oligohydramnios sequence, no additional malformations were noted in this female fetus. The de novo autosomal 6p/19q translocation was confirmed in a postmortem fibroblast culture of the right lung. The present observation of this de novo autosomal 6p/19q translocation with breakpoints at 6p23.1 and 19q13.4, respectively, associated with severe pyeloureteric junction obstruction as the sole severe fetal anomaly, indicates, in view of the findings of Izquierdo et al. (1992), that attention should be focussed on the 6p23.1 band in the further search for the precise location of the autosomal dominant hereditary hydronephrosis gene.
and the antigen identified by antibody, as the "serological H - Y " or "serologically detectable male" (SDM) antigen (Simpson et al. 1987). SDM (H-Y) antibodies are raised by sensitizing female rodents with skin grafts or lymphoid cells from syngeneic males. Typing for SDM is then accomplished by absorption of SDM antibody and testing of the absorbed antibody for residual activity on male cells or cell extracts. In mammals, SDM antisera are absorbed by male cells to a greater extent than they are by female cells (Wachtel et al. 1974). There appear to be at least two SDM antigens. One is an integral part of the membrane of male cells and one is a soluble factor secreted by the Sertoli cells of the testis (Zenzes et al. 1978b). It is remarkable that testis-secreted SDM can sex-reverse ovarian cells, causing them to form tubular structures in slow rotation cultures. This effect is blocked by H-Y antiserum (Mtiller and Urban 1981; Zenzes et al. 1978 a). These and other similar data have been taken to imply a role for Sertoli-cell-secreted SDM in the development of the mammalian testis (Ohno et al. 1979; reviewed in Wachtel 1983), although occurrence of soluble SDM could be secondary to the induction
Reference Izquierdo L, Porteous M, Paramo PG, Connor JM (1992) Evidence for genetic heterogeneity in hereditary hydronephrosis caused by pelvic-meteric junction obstruction, with one locus assigned to chromosome 6p. Hum Genet 89:557-560
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H-Y (SDM) antibody specifically binds Miillerian inhibiting substance Ulrich Miiller 1,2, Stephen S. WachteP, Vikram L. Jaswaney 3, Ellen H. Goldberg 4 1Genetics Division, Children's Hospital, Boston, MA 02115, USA 2 Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA 3Division of Reproductive Genetics, Department of Obstetrics and Gynecology, University of Tennessee, Memphis, TN 381, USA 4 Department of Microbiology, School of Medicine, The University of New Mexico, Albuquerque, NM 87131, USA
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Received: 18 September 1992 / Revised: 14 December 1992 hCG ",
H-Y ("male") antigens are defined by graft rejection (Eichwald and Silmser 1955), T cell cytotoxicity (Goldberg et al. 1973), and antibody (Goldberg et al. 1971). Evidently, the H - Y antigen identified by graft rejection is the same as that identified by T cell cytotoxicity but different from the H-Y antigen identified by antibody (Mtiller 1981). The antigen identified by graft rejection and T cell cytotoxity is referred to as the "H-Y transplantation antigen" Correspondence to: U. MiJller, Institut ftir Humangenetik, JustusLiebig-Universit~it, Schlangenzahl 14, W-6300 Giessen, Germany
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Fig. 1. Dose response curves. Reaction of monoclonal SDM antibody with MIS, two sources of soluble SDM (TS testis supernatant; TM-4 secretion products from primary cultures of Sertoli cells in serum-free conditioned medium) (Brunner et al. 1984), and hCG, an unrelated molecule. Total volume plated including antigen was 100 p.l per well. The antibody was biotinylated according to Brunher et al. (1984) and diluted l/2. At 10 gg/ml antigen or protein dilution (not shown), the optical density (OD) scores were: MIS 1.67; TS 2.5; TM-4 0.67; hCG 0.04. C denotes control scores: empty wells, antibody only, substrate only, respectively
