J. Rogers Byrd

Etiologies and subsequent reproductive performance of 100 couples with recurrent abortion.

From 1968 through 1977, 100 couples with documented recurrent reproductive failure were evaluated in the reproductive endocrine unit of the Medical College of Georgia. All couples underwent cytogenetic studies, radiologic evaluation of the Mullerian system, and timed endometrial biopsy. Recurrent pregnancy wastage was found to be associated with genetic disorders in 25 couples, Mullerian anomalies in 15, endocrine anomalies in 23, and negative findings in 37. The subsequent reproductive performance of each group is reviewed.

Delayed sexual development: A study of 252 patients

A series of 252 patients with abnormalities of pubertal development are reported. Ovarian failure, followed by Rokitansky syndrome and then physiologic delay, are the most frequently encountered etiologies. Other etiologies are diverse and numerically less frequent. The average age of presentation, patients height, somatic anomalies, diagnostic errors, and subsequent reproductive potential of each diagnostic group are reported. Only 35 (14%) of all patients presenting with abnormalities of pubertal development had subsequent normal reproductive potential. All of these patients were in the physiologic delay category.

The spectrum of gonadal dysgenesis: A clinical, cytogenetic, and pathologic study

Thirty-one patients with anatomical verification of the diagnosis of gonadal dysgenesis have been assessed as to possible correlations between clinical, cytogenetic, and histologic findings. No significant differences in histopathology were detected. Characteristically, histologic sections exhibited fibrous stroma and. mesonephric remnants with sporadic occurrence of Leydig or hilar cells. On the other hand, clinical and cytogenetic findings were quite variable. The clinical spectrum included patients of short, normal, and tall stature, some with and some without associated somatic anomalies. Among the 31 patients, cytogenetic studies revealed eleven different sex chromosome patterns including normal XX complements. There appeared to be some correlation between the amount of genetic privation and the incidence of somatic anomalies. Analysis of all data has led to the conclusion that most cases of gonadal dysgenesis may be diagnosed on the basis of clinical and cytogenetic findings alone. However, of special interest are a smaU minority of patients who require gonadal visualization for definitive diagnosis and accurate prognosis.

Cytogenetic Findings in Fifty-Five Couples with Recurrent Fetal Wastage

Balanced chromosomal translocations in parents and Mullerian abnormalities constitute defined causes of reproductive wastage. Fifty-nine couples with histories of recurrent abortion with or without fetal malformations were evaluated with cytogenetic studies and gynecography. In 44 of the couples with pure abortion histories of two or more spontaneous abortions, three (6.8%) balanced carrier parents were identified. In 11 couples with a mixed history of abortion plus fetal malformation, 3 (27.3%) had balanced translocations in one of the parents. The over-all incidence of Mullerian abnormalities in the group of 59 patients was 11.9%.

Phenotypic and Cytogenetic Findings in Eighty-Two Patients with Ovarian Failure—Changing Trends * †

Eighty-two patients with primary ovarian failure were evaluated clinically and cytogenetically. Sex chromosome privations were present in 52 individuals (chromosomally incompetent ovarian failure [CIOF]). A normal chromosomal constitution was present in 30 individuals (chromosomally competent ovarian failure [CCOF]). Limited estrogenic function (menses) occurred in 11.5% of the CIOF group and 40% of the CCOF group. The phenotypic features of each group are detailed in relation to chromosomal constitution, stature, estrogenic ridge function, incidence of dysgenetic tumors, and cardiovascular renal malformations. The increasing percentage of patients with CCOF due to possible diverse etiologies is noted and discussed.

Twins discordant for 46,XX gonadal dysgenesis.

This case report describes twin sisters, one with rudimentary streak gonads and the other with normal ovarian function. Both siblings had normal 46, XX karyotypes, and zygosity testing indicated that they were identical twins. Discordance of identical twins for 46, XX pure gonadal dysgenesis suggests that environmental factors may be a causative factor in some of the karyotypically normal 46,XX forms of gonadal dysgenesis.

Familial gonadal dysgenesis.

A case study of gonadal dysgenesis in 3 sisters is presented. The subjects were examined because of failure of the menarche sexual infantilism deafness and speech defects. All had positive buccal smears and a normal 46:XX karyotype. Vaginal cytology revealed a castrate type of specimen. Streak gonads were found upon laparotomy. Cyclic estrogen-progestogen therapy successfully promoted withdrawal uterine bleeding breast development growth of pubic and axillary hair and maturation of external genitalia. A primary interference in ovarian histogenesis is considered as a possible etiology.

Absence of the testicular determining factor gene SRY in XX true hermaphrodites and presence of this locus in most subjects with gonadal dysgenesis caused by Y aneuploidy

OBJECTIVES The purpose of our study was to discover whether the testicular determining factor gene SRY (sex-determining region on Y) is present or absent in XX true hermaphrodites and in subjects with gonadal dysgenesis caused by Y aneuploidy. STUDY DESIGN We screened five XX true hermaphrodites and 24 subjects with gonadal dysgenesis caused by Y aneuploidy for the presence or absence of SRY. With the polymerase chain reaction technique, the sequence coding the 80 amino acid-conserved motif was amplified. The 0.9 kb Hincll pY53.3 subclone, which covers the open reading frame of SRY, serves as a probe for Southern blot analysis. RESULTS Test results for all five XX true hermaphrodites were negative for SRY. Conversely, 22 of the 24 individuals with 45,X/46,XY gonadal dysgenesis were positive for SRY, including the 10 subjects with only bilateral streak gonads. CONCLUSIONS The absence of SRY in XX true hemaphrodites and the presence of SRY in 10 subjects with 45,X/46,XY constitution who harbored only bilateral streak gonads seem to indicate that multiple genes are involved in gonadal differentiation.

Use of two different deoxyribonucleic acid probes to detect Y chromosome deoxyribonucleic acid in subjects with normal and altered Y chromosomes

Four experiments evaluated the sensitivity and specificity of molecular techniques to detect human Y chromosome deoxyribonucleic acid. In experiment I, electrophoretic separation of normal male deoxyribonucleic acid fragments after digestion with endonuclease Hae III revealed two male-specific bands of 3.4 and 2.1 kilobase (kb). These bands were not visible if the fraction of male deoxyribonucleic acid in mixed samples was less than 0.3. In experiment II, by means of a repetitive copy Y deoxyribonucleic acid probe (pS4) mapped to Yq12, a male-specific 2.3 kb band was detectable in mixtures of 2.5 ng of male deoxyribonucleic acid and 997.5 ng of 45,X female deoxyribonucleic acid. In experiment III, hybridization with the pS4 probe was performed on the deoxyribonucleic acid of 20 subjects with a normal or a variant Y chromosome. In experiment IV, deoxyribonucleic acid from the same subjects was hybridized to a single copy probe (4B-2) mapped to the Yq11 region. Deoxyribonucleic acid from category A subjects (n = 8) with cytologically normal Y chromosomes hybridized to both deoxyribonucleic acid probes. Deoxyribonucleic acid from category B subjects (n = 2), including a variant Y chromosome that was negative for Q-banding but positive for C-bands, hybridized with the distal pS4 and proximal 4B-2 probes. Deoxyribonucleic acid from category C subjects (n = 10) with variant Y chromosomes uniformly negative for Q- and C-bands, did not hybridize with the pS4 probe. Deoxyribonucleic acid from three of the 10 category C subjects did hybridize to the more proximal sequence-detecting 4B-2 probe. Deoxyribonucleic acid from the remaining seven subjects in category C did not hybridize with either of the deoxyribonucleic acid probes.

Use of human α-satellite deoxyribonucleic acid to detect Y-specific centromeric sequences

The Y alphoid deoxyribonucleic acid probe Y97 has proved to be specific for the human Y centromere and to define a Y-specific 5.5 kb Eco RI fragment. Three experiments were designed to evaluate the sensitivity and the specificity of this Y alphoid probe Y97. In the first experiment the centromeric Y-specific 5.5 kb Eco RI fragment was clearly seen in the mixture of 0.050 microgram of male DNA with 4.950 micrograms of female DNA (1%). In the second experiment the same dilutional study was applied to the Yq11-related probe 4B-2 for comparison purpose. In the third experiment, hybridization with the Y97 probe was performed on 20 subjects with mosaic cell lines containing a cytogenetically identifiable Y (n = 10) and a cytogenetically unidentifiable minute (n = 10) fragment. Nineteen of the 20 subjects demonstrated the Y-specific 5.5 kb Eco RI hybridization band with the centromeric Y97 probe. These experiments demonstrated the utility of the Y97 probe to consistently identify cytogenetically altered Y chromosome fragments and confirm the mapping of the alphoid repeat sequences to the centromeric region of the Y chromosome.