James C. Detter

Inherited variations in human phosphohexose isomerase.

1. The elctrophoretic pattern of phosphohexose isomerase has been examine in the blood of 3397 unrelated individuals from several different populations groups.

6-Phosphogluconate Dehydrogenase: Hemizygous Manifestation in a Patient with Leukemia

In a study of 41 patients with chronic myelocytic leukemia, two were found to have the 6-phosphogluconate dehydrogenase heterozygous phenotype A-B, and two had the phenotype characteristic of PdB homozygosity. Since one of the two with PdB homozygosity was the mother of two children with the A phenotype, it was presumed that she carried a PdA gene not expressed in her blood cells. his was confirmed by electrophoretic analysis of her fibroblasts, which had the A-B phenotypic pattern. Gene deletion is considered to be the most likely explanation.

A screening protocol for a prenatal population at risk for inherited hemoglobin disorders: Results of its application to a group of Southeast Asians and blacks

Several inherited hemoglobin disorders are present among certain racial subgroups of the United States population, particularly among blacks and Southeast Asians. Many of these disorders are unfamiliar to the obstetrician-gynecologist but may have important implications for care in pregnancy, including genetic counseling and prenatal diagnosis. A simple, effective screening tool was devised for detection of thalassemias and hemoglobinopathies in a prenatal clinic population. Use of the tool resulted in diagnosis of a hemoglobin disorder in 20% of a group of black patients; diagnoses included alpha-thalassemia trait, beta-thalassemia trait, hemoglobin C trait, hemoglobin S/C disease, hemoglobin S trait, sickle cell anemia, and hemoglobin Lepore. In a group of Southeast Asian patients, 39% had a hemoglobin disorder, including alpha-thalassemia trait, beta-thalassemia trait, hemoglobin E disease, and hemoglobin H disease. Implications for care are discussed.

Genetic markers in chronic myelocytic leukaemia: evidence opposing autosomal inactivation and favouring 6-PGD-Rh linkage.

The possibility that there is random fixed inactivation a t autosomal loci, similar to that which effects major portions of the X chromosome, has been put forth by several workers (reviewed by Beutler, 1964). The best evidence in support of such an occurrence in autosomes is provided by the apparent inactivation of genes which control immuno-globulin synthesis (Pernis & Chiappino, 1964). Evidence against inactivation has been found for the loci controlling the synthesis of haemoglobin chains (Beutler, 1964) as well as the enzymes, lactate dehydrogenase, phosphoglucomutase,, and the branch chain amino acid decarboxylase (Davidson, Glen-Bott & Harris, 1965; Sigman & Gartler, 1966). The opportunity to look for inactivation a t several other autosomal loci was provided by the recent observation that chronic myelocytic leukaemia (CML) arises in a single marrow stem cell, i.e. the disease has a clonal origin (Fialkow, Gartler & Yoshida, 1967; Fialkow et al. 1969). Thus, one would expect that if a patient with CML were heterozygous a t any locus undergoing inactivation, that locus would have hemizygous expression in the CML cells but heterozygous expression in other tissues. A further advantage in studying CML patients is derived from the fact that their erythrocyte, granulocyte, and platelet precursors contain the Philadelphial (Phl) chromosome. This finding not only supports the concept of a clonal origin of CML, but also provides an opportunity to perform deletion mapping, since the Phl chromosome (number 22 (Caspersson et al. 1970)) lacks about 40 yo of its DNA. Thus, a hemizygous phenotype would also be observed in the CML cells of a heterozygote if the locus involved was situated on the deleted portion of the Phl chromosome and if that portion was not translocated onto another chromosome. In a previous paper (Fialkow et al. 1969) we reported finding a hemizygous 6-PGD phenotype in the CML cells of one patient whose cultured skin and inheritance studies both showed her to be heterozygous at the 6-PGD locus. Deletion was considered to be the most likely explanation. In this communication an extension of our previous study we provide data which support that deletion hypothesis and strengthen the suggestion of Weitkamp, Guttormsen & Greendyke (1969, 1970) that there is genetic linkage between the 6-PGD and Rh loci. In addition, our data demonstrate the absence of fixed inactivation a t a number of autosomal loci.