Miriam G. Wilson

Genetic and clinical studies in 13 patients with the Wolf-Hirschhorn syndrome [del(4p)]

SummaryClinical and cytogenetic studies are reported on 13 patients with Wolf-Hirschhorn syndrome. The oldest of the living twelve probands is 24 years of age. Three of these patients has a translocation involving the short arm of chromosome 4, and in one of these the anomalous chromosome was inherited from the father. Another three patients were believed, on the basis of GTG-staining, to have a translocation although the origin of the translocated chromatin could not be identified. In the remaining seven patients the anomalous chromosome appeared to be a simple deletion, although in two cases a translocation could not be reled out. Cytogenetic studies in these patients suggest that the critical deletion involved in Wolf-Hirschhorn syndrome is within 4p 16.

Chromosomal anomalies in patients with retinoblastoma

Karyotypes from 50 persons with retinoblastoma confirmed by histopathological examination were studied by conventional staining and Giemsa‐banding techniques. Two chromosomal anomalies were found. An interstitial deletion of the long arm of No. 13 chromosome was identified by Giemsa‐banding in the karyotypes from a boy with unilateral retinoblastoma. Another boy with unilateral tumor had a karyotype of 47, XXY. These findings provide additional evidence that a deletion of chromosome No. 13, most likely involving band 13q14, is associated with the development of retinoblastoma. In conjunction with other reports, our findings also suggest that retinoblastoma may be found more frequently in children with chromosomal aneuploidy.

Needle puncture of fetus: a complication of second-trimester amniocentesis.

Needle puncture of the fetus has rarely been reported with midtrimester amniocentesis. This paper contains the report of five cases of needle scars in infants born after second-trimester amniocentesis for prenatal diagnosis of fetal genetic disorders. Since this complication may be more frequent than has been previously believed, there is the possibility that damage to the fetus may occur. It is suggested that the products of all abortions and all live-born and stillborn infants delivered following amniocentesis should be examined for evidence of injury.

Inherited partial duplication of chromosome No. 15

A boy with unusual facial appearance and mental retardation was found to have duplication for the distal half of the long arm of chromosome No. 15 and possibly deficiency for the distal end of the long arm of No. 21. The chromosome abnormality was inherited from his mother, who had a translocation involving chromosomes Nos. 15 and 21. Giemsa-banding localized the break point in chromosome No. 15 just distal to the intense band at the midportion of the long arm. The break point in chromosome No. 21 appeared to be at the distal end of the long arm. The difficulty encountered in cytogenetic analysis of the propositus with conventional staining, the importance of chromosome analysis of the parents, and the application of differential staining techniques are also presented.

Giant satellites or translocation

An infant with craniostenosis and retardation was found to have giant satellites on chromosome No. 13. Trypsin-Giemsa banding studies demonstrated, in addition, a partially deleted short arm of chromo

Two alpha-glucosidases in cultured amniotic fluid cells and their differentiation in the prenatal diagnosis of Pompe's disease.

A sensitive fluorometric assay utilizing 4-methylumbelliferyl-alpha-D-glucopyranoside has been developed for the determination of alpha-glucosidase. The enhanced sensitivity was achieved by increasing the solubility of the substrate with a water miscible organic solvent. With this system, cultured amniotic fluid cells were found to have two major forms of alpha-glucosidase with somewhat overlapping acidic pH optima; one with pH optimum at 4.5 is deficient in Pompes disease (type II glycogenosis), while one with pH optimum at 6.0 is not affected in this disease. Specificity for the pH 4 form of alpha-glucosidase was achieved by exploiting the greater thermal lability of the pH 6 enzyme. The pH 6 form of the enzyme was also detectable in freshly prepared extracts of cultured fibroblasts. The procedure is direct and simple and has been applied to the prenatal diagnosis in two pregnancies at risk for Pompes disease.

Decreasing mosaicism in Down's syndrome

A girl with trisomy‐21/normal mosaicism has been abserved for approximately 10 years. Her appearance is reminiscent of, but not typical for Downs syndrome, and her intellectual abilities are impaired but not to the same severe degree expected in Downs syndrome. These observations are consistent with the belief that, in persons ascertained by clinical resemblance to Downs syndrome, mosaicism with a normal cell line may dilute the typical appearance of Downs syndrome. The cytogenetic studies performed longitudinally demonstrated a significant decrease in the proportion of blood lymphocytes showing the trisornic line. The maximal decrease occurred in the first year of life. A direct preparation from the bone marrow and a fibroblast culture at 2.5 months showed 3 and 4 % trisomic cells, respectively, corresponding to the level of trisomic cells from the blood cultures during the second year of life.

Inadvertent rubella immunization in pregnancy

Abstract Sixty women inadvertently immunized with live rubella vaccine within 90 days before or during pregnancy have been studied. Only 9 of the women were known to be susceptible to rubella prior to immunization. Of these, 6 had normal infants, 1 had a therapeutic abortion, and 2 had spontaneous abortions. Of the remaining 51 women with unknown immune status, 33 were delivered of apparently normal infants and 14 had therapeutic (13) or spontaneous (1) abortions. In addition, the outcome of 4 pregnancies was as follows: one set of twins, a term infant who died at 5 days from hyaline membrane disease, a small premature infant who died, and an infant with a heart murmur. Of the pregnancies that were terminated, in 2 instances rubella virus was isolated from tissue removed at therapeutic abortion. In one instance the virus is probably “wild,” representing natural infection. In the other instance, the virus appears to be of vaccine origin. Histologic examination of abortus tissue revealed nonspecific inflammatory changes in 2 of the known rubella-susceptible women, in 6 in whom the susceptibility was unknown, and in 2 of 5 products of conception obtained from nonimmunized women having therapeutic abortions. No definite statement can be made regarding the embryopathic potential of the rubella vaccine from these data.

Sister chromatid exchanges and chromosome aberrations in fibroblasts from patients with retinoblastoma.

SummaryThe frequencies of sister chromatid exchanges (SCEs) and chromosome breaks were investigated in five diploid fibroblast strains derived from three patients with deletion 13[del(13)] retinoblastoma, one patient with a hereditary form of retinoblastoma, and one trisomy 13. The fibroblasts with del(13)(q14q22) showed slightly increased SCEs (at a P level of 5–10%), but the others, including del(13)(q12q14), the hereditary form of retinoblastoma, and trisomy 13, did not have increased SCEs as compared to normal controls. No increase in chromosome breaks was found in these fibroblasts. The results suggest that retinoblastoma is not associated with spontaneous increased chromosomal instability.

Trisomy 13 in Two Infants with Cyclops

Two infants with cyclops malformation were born at the University of Southern California Medical Center during the past three years. The karyotypes of both infants demonstrated an extra chromosome No. 13: one with 47,XX,+13 and one with 46,XX,-14,+t(13q14q). The physical findings, karyotypes with trypsin-Giemsa banding, and association of trisomy 13 syndrome with cyclops malformation are presented.