Elizabeth Dorus

Relatives of unipolar and bipolar patients have normal pursuit.

Impaired smooth pursuit eye movements are significantly less prevalent among the first-degree relatives of patients who have major affective disorders than among the first-degree relatives of schizophrenics. The distribution of normal and abnormal smooth pursuit among the relatives of unipolar and bipolar patients does not differ from that of normal individuals having no family history of major psychosis. Smooth pursuit impairment is thus specific to relatives of schizophrenic patients and is not characteristic of relatives of patients with major affective disorders.

Genetic control of platelet monoamine oxidase activity: Studies on normal families

Abstract Some groups of psychiatric patients differ from normal individuals with respect to mean platelet monoamine oxidase (MAO) activity. Twin studies indicate that genetic factors contribute to the considerable interindividual variability in the activity of this enzyme. To evaluate the degree of genetic control, we measured platelet MAO activity in 255 normal adult members of 112 families. Between-family variance was significantly greater than within-family variance, as would be expected. Parent-offspring and sibling-sibling correlations indicated that genetic factors control platelet MAO activity to a substantial extent.

Clinical, pathologic, and genetic findings in a case of 46,XY pure gonadal dysgenesis (Swyer's syndrome): II. Presence of H-Y antigen

Evidence that expression of histocompatibility-Y (H-Y) antigen on human cells is determined by a Y-linked gene is provided by data demonstrating that male subjects with two Y chromosomes have higher antigen levels than male subjects with one Y chromosome. The widespread evolutionary conservation of H-Y antigen and its association with the Y chromosome suggest that the antigen has a specific, crucial function. We surmise that this function is the differentiation of the embryonic gonad into whichever mature gonad, testis or ovary, typifies the heterogametic sex of each species. Of particular interest are individuals whose gonadal sex does not correspond to their somatic genotype. In the present article, we report positive results in the first case of 46,XY pure gonadal dysgenesis (Swyers syndrome) to be typed for H-Y antigen. This case suggests that the presence of H-Y antigen may not be sufficient to complete masculinization of the embryonic mammalian gonad. Alternatively, a mutant gene may govern expression of a cell surface component which cross reacts with H-Y antigen but which lacks the ability to function in the virilization of the gonad.

Reduced platelet MAO activity and vulnerability to psychiatric disorders

Platelet monoamine oxidase (MAO) is a genetically controlled mitochondrial enzyme that metabolizes amines in the brain by deamination. We investigated the relationship between MAO activity and the presence or absence of psychopathology by determining MAO activity and the psychiatric diagnosis in 61 first-degree relatives of 31 patients with bipolar (manic-depressive) illness. Relatives who themselves were diagnosed as having bipolar I illness or alcoholism had a significantly lower mean MAO activity level than did other relatives or 255 normal individuals. These findings indicate that a relationship exists within pedigrees between MAO activity and psychiatric disorders. Reduced MAO activity may play a role in vulnerability to some types of psychopathology.

Genetic control of human plasma creatine phosphokinase activity

Plasma creatine phosphokinase (CPK) activity was determined in 14 monozygotic (MZ) and 14 dizygotic (DZ) twin pairs. The heritability indexes calculated for plasma CPK activity indicated support for the hypothesis that plasma CPK activity is under some genetic control. This finding is discussed in relation to various diseases in which plasma CPK activity is increased.

Clinical, pathologic, and genetic findings in a case of 46, XY pure gonadal dysgenesis (Swyer's syndrome)

Cytogenetic, pathologic, and clinical studies were conducted on a phenotypically female patient with primary amenorrhea and infertility. Analysis of blood cultures with routine and Giemsa-banded preparations indicated that the chromosomal complement of the patient was 46,XY. Buccal and peripheral blood smears prepared for fluorescent analyses confirmed the presence of a single F-body (Y chromosome). Pathologic examination of tissues removed at total hysterectomy and bilateral salpingo-oophorectomy revealed a gonadoblastoma of the right gonad, dysgerminoma of the left gonad, and an infantile hypoplastic uterus. The data were consistent with a diagnosis of 46,XY pure gonadal dysgenesis (Swyers syndrome).

A ring 14 chromosome with deleted short arm

SummaryWe report a 46,XX,r(14) karyotype in a female infant having craniofacial dysmorphology, a seizure disorder, and developmental retardation.

A reciprocal translocation (X;11) in a female with gonadal dysgenesis.

A 24‐year‐old female patient was referred for evaluation of primary amenorrhea. Endocrine studies showed elevated gonadotropins, consistent with gonadal failure. At laparoscopy, a normal nulligravid uterus, normal fallopian tubes, and bilateral streak gonads were observed. Histologic studies showed that the left gonad consisted entirely of fibrous tissue, confirming the presence of streak gonads. Chromosome banding studies of peripheral blood and cultures of tissue from the left gonad demonstrated a 46, X, rcp(X;11)(q22;q13) karyotype. A review of reports of X‐autosome reciprocal translocations indicated that abnormal gonadal development is associated with break‐points in the mid‐region of the long arm of the X chromosome.

Red-cell lithium transport and affective disorders in a multigeneration pedigree: Evidence for genetic transmission of affective disorders

We determined if a polymorphism at a major gene locus contributing to variability in the distribution of lithium (Li) across the red cell membrane is associated with vulnerability to affecfive disorders within a multigeneration pedigree. The variability in the ratio of intracellular to extracellular Li concentration (Li ratio) in vivo is primarily determined by variability in a lithium-sodium (Li-Na) counterflow mechanism; the Li ratio and Li-Na counterflow vary inversely (Duhm et al. 1976; Pandey et al. 1978). Dorus et al. (1983) demonstrated that interindividual variability in the Li ratio in vitro is determined both by a major autosomal gene locus and by multifactorial inheritance. Boerwinkle et al. (1983) found evidence for a major gene locus in the control of Li-Na counterflow. Some, but not all, investigators report significantly elevated Li ratios or lowered Li-Na counterflow values among bipolar patients (Rybakowski et al. 1978) and among first-degree relatives of bipolar patients who themselves have a history of an affective disorder (Dorus et al. 1979; Mendlewicz and Verbanck 1981). Dorus et al. (1983) provided evidence for a major gene locus that is involved in the transmission of both variability in the Li ratio and vulnerability to affective disorders among first-degree relatives of bipolar patients. Egeland et al. (1984), however, found no relationship between variability in Li transport measures and a history of an affective illness in four Amish pedigrees. The investigators note the considerable genetic and environmental homogeneity of the Amish population. Such homogeneity could affect the subtypes of affective disorders found in these pedigrees. Waters et al. (1983) found that variability in phloretin-sensitive Li-Na counterflow was not related to history of an affective disorder among relatives of bipolar patients. The authors observed, however, substantial intraindividual variability in their serial determinations of counterflow.

Personality correlates of platelet monoamine oxidase activity and red cell lithium transport

Platelet monoamine oxidase (MAO) activity and the ratio of red cell to plasma lithium concentrations (Li ratio) may be important in the pathophysiology of, and genetic vulnerability to, some psychiatric disorders. By using the Clinical Analysis Questionnaire, we assessed personality correlates of MAO activity and the Li ratio in vitro in a sample of psychiatrically normal adult women. We found that there were correlates of each variable, and a unique constellation of personality traits when the two variables were considered simultaneously.