Cecil B. Jacobson

Intrauterine diagnosis and management of genetic defects

Abstract Amniotic fluid samples were obtained at early stages of pregnancy (56 before 20 weeks), when therapeutic termination of pregnancy could be performed should a genetic error be documented. Tissue culture growth was obtained in 62 of 74 samples with chromosomal analysis and established cell lines produced for genetic counseling. Sex chromatin was shown to be correlated with karyotypic and phenotypic sex when limited to the midgestational stage (10 to 34 weeks). A classification of the clinical conditions exhibiting a genetic risk of sufficient magnitude to warrant intrauterine analysis is given.

Intrauterine Diagnosis of the Hurler and Hunter Syndromes

Abstract Prenatal diagnosis was accomplished for two women who had previously borne children affected with genetic disorders of mucopolysaccharide metabolism — the Hurler syndrome (autosomal recessive) in one case and the Hunter syndrome (X-linked recessive) in the other. Amniotic fluid, which contains fetal cells, was obtained by transabdominal amniocentesis. After culture in vitro, the amniotic fluid cells displayed two characteristics (a distinctive kinetic pattern of radioactive sulfate incorporation into mucopolysaccharide and metachromatic staining with toluidine blue) that are also exhibited by cultured skin fibroblasts derived from patients with these metabolic disorders.

Fabry's Disease: Antenatal Detection

A procedure is described for the intrauterine detection, at the 17th week of gestation, of a male fetus afflicted with Fabrys disease. The validity of this determination was substantiated by multiple enzyme and lipid analyses of tissue specimens obtained from the afflicted fetus. Fabrys disease may now be included with other X-linked metabolic deficiency diseases that are amenable to precise genetic counseling, through carrier identification, and the monitoring of ensuing pregnancies.

Autosomal Trisomy in a Chimpanzee: Resemblance to Down's Syndrome

An infant chimpanzee (Pan troglodytes) with clinical, behavioral, and cytogenetic features similar to those in Downs syndrome is described. The infant shows retarded growth rate, congenital abnormalities, retarded neurologic and postural development, epicanthus, hyperflexibility of the joints, muscle hypotonia, and trisomy of a small acrocentric chromosome.

Beta-galactosidase in tissue culture derived from human skin and bone marrow. Enzyme defect in GM1 gangliosidosis.

Extract: β-Galactosidase activities were determined in fibroblast preparations derived from the bone marrow and skin of a patient with GM1 gangliosidosis and from 11 control subjects. Two β-Galactosidase substrates were employed in these studies: ganglioside GM1, labled with tritium in the terminal galactose by a new procedure, and o-nitrophenly-β-galactopyranoside. The GM1-β-galactosidase activity in the cells of the patient was reduced 17- to 30-fold compared with the activity in the cells of the control subjects; also, the cells of the patient exhibited an 11- to 30-fold depression in onitrophenyl-β-galactosidase activity (ONP-β-galactosidase). These results demonstrated that fibroblasts cultured from an affected subject might be employed for diagnostic purposes. The GM1-and o-nitrophenyl-β-galactosidase activities of fibroblasts cultured from amniotic fluid have also been determined; o-nitrophenly-βgalactosidase activities ranged from 61 to 153 units/106 cells and the GM1-βgalactosidase activities varied between 45 and 95 units/108 cells.Speculation: Determination of GM1-β-galactosdase activity in fibroblasts cultured from skin may permit the detction of individuals heterozygous for GM1 gangliosdosis. The presnce of a β-galactosidase capable of releasing the terminal galactose from ganglioside GM1 in fibroblasts derived from amniotic fluid offers a basis for possible intrauterine diabnosis of GM1 ganagliosidosis.

Prenatal Diagnosis of Cystinosis

Abstract We diagnosed cystinosis in an 18-week-old fetus on the basis of an increased content of nonprotein cystine in cultured amniotic-fluid cells. These cells did not contain cystine crystals, a...

Neoplasms of dysgenetic gonads.

P R E v 1 0 Is classifications of patients who have had gonadal maldevelopmcnt have been based upon clinical findings, on morphology of the external genitals, on appearance of the gonads. and/or upon chromosomal constitution (karyotype) Reliance on one or the other of the above categories has resulted in an unsatisfactory system of classification which has persisted to the present time, despite the efforts of a few investigators to construct a standardized classification, or, at least, to dr\ise a more satisfactory terminology.‘-” I n order to better evaluatr the incidence and types of neoplasms associated with aberrant gonadal development, it is important to define some of the type‘s of ,qonadal maldevelopment that arc rerognixed: and to relate them to the classification proposed by other authors.

Some cytogenetic aspects of habitual abortion

Abstract An interdisciplinary study of the genetics in spontaneous abortion is described and the chromosomal complement of 35 first trimester abortions reported. In these cases it was found that early abortions have a higher incidence of chromosomal abnormalities (25 per cent below 13 weeks). A high number of the abnormal embryos (5 of 8) were found to be monosomic; two of these showed a double monosomy (X + autosome). Monosomic embryos aborted earlier and showed grossly abnormal morphology. A possible genetic explanation for the susceptibility of monosomic embryos toward abortion is advanced and the differences between two types of chromosomal anomalies is described.

GENETIC COUNSELING IN OBSTETRICS AND GYNECOLOGY

It is the increasing responsibility of the obstetrician and gynecologist to assume a role in genetic counseling. He is ideally suited for this by the very nature of his specialty, since his contact with patients covers the entire life span of womanhood. It is hoped that he will make an effort to supplement his treatment with counseling, early recognition and diagnosis of abnormal conditions and treatment of these deformities. It is suggested that by obtaining an adequate history and performing a thorough physical examination of mothers during prenatal care, and of the babies at the time of delivery, a great step may be taken in this direction.