Unbalanced translocation 46,XY,-15,+der(22)t(15;22)(q13;q11)pat: case report and review of the literature.

We present a boy with a rare unbalanced translocation 46,XY,-15,+der(22),t(15;22)(q13;q11) pat. Previous reports of similar chromosome findings mention only the Prader-Willi phenotype. At birth, his manifestations included severe hypotonia and lethargy, (typical of deletion of 15pter----q13); hypertelorism, down-slanting small palpebral fissures, preauricular tags, long philtrum (typical of duplication of 22pter----q11); severe laryngotracheomalacia, and proximal implantation of the thumb. In a review of the literature on chromosome abnormalities involving duplication of 22q11 the associated clinical phenotype consists of mild mental retardation, microcephaly, hypotonia, hypertelorism, down-slanting palpebral fissures, a long philtrum, cleft or highly arched palate, and ear abnormalities. Preauricular pits or tags are common. Cardiovascular defects, renal and genital problems and dislocated hips are frequently present. Anal atresia and colobomata are mainly seen in cat-eye syndrome, the phenotype associated with idic 22q11. Our findings indicate that patients with unbalanced t(15;22) can have manifestations of the dup 22q11, in addition to the previously reported Prader-Willi phenotype, even if the duplicated segment is small.

Acardius anceps with evidence of intrauterine vascular occlusion: report of a case and discussion of the pathogenesis.

An acardiac anomaly (holoacardius anceps) showed advanced development of the head and lower body parts in the absence of all thoracic and upper abdominal viscera. Large vascular anastomoses in the vertebral canal formed the only blood supply to the head. The two-vessel umbilical cord of the acardius contained calcified mural thrombi in both vessels. Severe fetal hydrops resulted in an exceptionally large birth weight of 3720 g. Fibroblasts from the acardius showed chromosomal mosaicism. The surviving co-twin was remarkable for a widely patent ductus arteriosus, unilateral multicystic renal dysplasia, and a normal chromosome complement. The circumscribed absence of organ development in the thorax and upper abdomen of the acardius and the vascular anatomy with thrombosis of the umbilical vessels suggest that an occlusion of thoracic and abdominal vessels was significant in the development of this acardiac malformation and should be considered as a possible pathogenetic mechanism in similar cases of acardia.

Prenatal diagnosis of molybdenum cofactor deficiency by assay of sulphite oxidase activity in chorionic villus samples.

Molybdenum cofactor deficiency is characterized by the absence of sulphite oxidase, xanthine dehydrogenase and aldehyde oxidase, the three known enzymes in man that require the cofactor for their activity. Prenatal diagnosis of the deficiency may be performed by assay of sulphite oxidase activity in cultured amniocytes. However, the activity in amniocytes is low and large numbers of cells are required for reliable assessment. We show that sulphite oxidase is present at high levels in chorionic villi obtained at 10-14 weeks gestation and can be assayed directly in the biopsy sample without cell culture. This assay has been applied to two pregnancies at risk for molybdenum cofactor deficiency with successful diagnoses of an unaffected and an affected fetus.

Familial inheritance of a DXS164 deletion mutation from a heterozygous female.

Restriction-fragment-length-polymorphism analysis was used to examine a female who is segregating for Duchenne muscular dystrophy (DMD) and a deletion of the DXS164 region of the X chromosome. The segregating female has no prior family history of DMD, and she has two copies of the DXS164 region in her peripheral blood lymphocytes. The following two hypotheses are proposed to explain the coincidence of the DMD phenotype and deletion of the DXS164 region in her offspring: (1) she may be a gonadal mosaic for cells with two normal X chromosomes and cells with one normal X chromosome and an X chromosome with a deletion of the DXS164 region; and (2) she may carry a familial X;autosome translocation in which the DXS164 region is deleted from one X chromosome and translocated to an autosome. The segregation of DMD and the DXS164 deletion in this family illustrates the importance of extended pedigree analysis when DXS164 deletions are used to identify female carriers of the DMD gene.

Inherited chondrodysplasia punctata due to a deletion of the terminal short arm of an X chromosome.

We studied two families with an inherited deletion of the short arm of an X chromosome (Xp) in which affected male offspring have epiphyseal stippling in infancy (chondrodysplasia punctata), nasal hypoplasia, ichthyosis, and mental retardation. The presence of ichthyosis and the apparent pattern of X-linked recessive inheritance prompted investigation of the short arm of the X chromosome through studies of genetic markers and focused cytogenetic analysis. Biochemical studies suggested that there was a deletion of three genes previously mapped to the X-chromosome short arm, including the steroid sulfatase locus, the Xg locus, and the M1C2X locus. Prometaphase chromosomes demonstrated a deletion of Xp at p22.32 in the affected boys, in their obligate-carrier mothers, and in 11 of 25 women at risk as potential carriers. The women carrying the Xp deletion had normal gonadal function and fertility but were shorter than the noncarriers in their families (P less than 0.00001). These findings have implications for the genetic organization of this portion of the human X chromosome and demonstrate that small cytogenetic abnormalities may account for disorders with apparent mendelian patterns of inheritance.

Human chorionic gonadotropin maintains plasma progesterone at pregnancy levels in rhesus monkeys.

Peripheral plasma progesterone (P) levels in the rhesus monkey remain relatively constant both during the latter half of pregnancy and for long periods after fetectomy (removal of the fetus with the placenta left in situ) or ovariectomy. The constancy is maintained despite what appears to be reciprocal changes in the relative contributions of ovary and placenta. Placental regulation of the corpus luteum is likely, but it is not known if the corpus luteum responds to a gonadotropic stimulus in the later stages of pregnancy. In this study, we have investigated the effects of hCG administration in postdelivery monkeys (normally pregnant, fetectomized, ovariectomized and sham ovariectomized animals) and have determined if hCG administration maintains plasma P at pregnancy levels. hCG maintained P at pregnancy levels after surgical removal of the conceptus near term in both normally pregnant and previously fetectomized monkeys over a 7-day treatment period. hCG treatment after normal delivery maintained P levels in sham-ovariectomized but not in ovariectomized monkeys over an 8-day treatment period. The magnitude of the response to hCG declines over the treatment period in all groups except fetectomized monkeys, although hCG levels in the peripheral plasma are quite constant. These results indicate that the ovary of late pregnancy is fully capable of producing P at normal values and is responsive to this gonadotropin.

Effect of the fetal placenta and of a rabbit pituitary extract on plasma progesterone in fetectomized rabbits.

When fetuses and placentas were removed on Day 18 in normal pregnant rabbits, plasma progesterone levels declined rapidly to non-pregnant values within 48 h. This decline was largely prevented if only fetectomy was performed, leaving the placentas in situ, but not when the fetal components of the placentas were also removed. These results suggested that ovarian progesterone production was dependent upon trophic influences emanating from the fetal portions of the placentas. Ovarian progesterone production was maintained by an extract of rabbit pituitaries for at least 72 h after removal of fetuses and placentas.

Observations on progesterone production and clearance in normal pregnant and fetectomized rhesus monkeys (Macaca mulatta).

The metabolic clearance rate (MCR) and production rate (PR) of progesterone were measured in rhesus monkeys both before and during intravenous infusion of progesterone at rates which approximately doubled or tripled the peripheral plasma levels. The monkeys were normally pregnant or fetectomized and were studied during the second half of pregnancy. Raising the peripheral plasma levels did not significantly after the MCR or the PR of progesterone. We conclude that peripheral progesterone levels are not the factor which controls the PR of progesterone in rhesus monkeys.

An infant with trisomy 9pter yields 9q22 resulting from 3:1 segregation in a 46,XX t(1;9) (p36;q22) mother.

A newborn infant with a 47,XY,+ der(.),t(1;9) (p36;q22)mat chromosome complement and the clinical features of the 9p trisomy is described. A review of the reproductive histories of five cases with trisomy 9pter yields 9q21 or 22 indicate that the balanced translocation mothers of these infants may have as high as a 23% chance of producing a chromosomally unbalanced offspring due to 3:1 disjunction.

Metabolic clearance rates (MCR) and production rates (PR) plasma progesterone in pregnant and pseudopregnant rabbits.

Our studies were designed to determine whether changing peripheral progesterone levels in rabbits reflected changing metabolic clearance rates (MCR) or changing production rates (PR), or both. Plasma progesterone concentrations rise from nonpregnancy levels to peak values at the end of the first third of gestation and at midpseudopregnancy. In the pregnant rabbit, these decline slowly during the second third of gestation and then more rapidly until near nonpregnancy values are reached at term. Progesterone levels decline sharply during the second half of pseudopregnancy. During pregnancy and pseudopregnancy, we found only small variations in MCRs which cannot account for the approximately 10-fold increase in plasma progesterone concentrations. The increases can, however, be accounted for by changes in PRs which rose sharply after conception of hCG injection to 14-fold the nonpregnancy level on day 16 of gestation and 11-fold on day 7 of pseudopregnancy. These results indicate that changes in ovarian PRs are the major factor for the variations in peripheral progesterone levels during pregnancy and pseudopregnancy. The rabbit differs in this respect from the guinea pig, in which changing progesterone concentrations during pregnancy were shown to reflect sharply reduced MCRs. After a single injection of progesterone in 20-day pregnant rabbits, the disappearance of the steroid from the circulation consisted of two components; an initial phase during which progesterone disappeared rapidly (t1/2 = 2.4 +/- 0.2 min) followed by a slower rate of disappearance (t1/2 = 21.5 +/- 2.2 min).