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Summary Biochemical, cytochemical characteristics and electron microscopy subcellular distribution of neutrophil alkaline phosphatase (NAP) were analysed in blood and/or smear samples from 39 trisomy 21 patients (Down's syndrome) aged 11·5-18 years (mean 15·5 years) and 55 normal subjects aged 12-20·5 years (mean 17 years). All patients were karyotyped. NAP cytochemical procedures were carried out on all subjects: biochemical NAP determinations were made in 10 patients and 20 controls: ultrastructural electron microscopy of AP was performed in three patients and four normal subjects. Neutrophil alkaline phosphatase from patients with trisomy 21 displayed the following changes: (1) a significant increase of enzyme activity, (2) a high thermal lability of enzyme. Electron microscope morphology exhibited large deposits of NAP reaction product associated with the plasma membrane and intracellular main organelles, like phosphasomes. The NAP biochemical and cytochemical characteristics suggest that trisomy 21 neutrophils contain a nonspecific AP isoenzyme, closely related to the early placental form.

We report the case of a patient (followed from birth to 15 years) presenting with trisomy 12 mosaicism, and focus on the endocrine phenotype associating a pituitary malformation and ovarian abnormalities. We describe the dysmorphic features and their evolution, the growth retardation and ovarian symptoms. Complete growth hormone deficiency was confirmed on auxological data, stimulation test and was related to pituitary stalk interruption, diagnosed by magnetic resonance imaging. Effect of growth hormone treatment was satisfactory resulting in a normal adult height. She also presented premature thelarche associated with right ovarian hypertrophy (4 to 5 fold the volume of the left ovary) which remained constant until 15 years of age. Diagnosis of trisomy 12 mosaicism was made on skin and ovarian karyotypes. The possible relation between these endocine findings and some genes located on chromosome 12 involved in pituitary and ovarian development is discussed.

Immunoreactivity, cytochemical, immunocytochemical characteristics and subcellular distribution of neutrophil alkaline phosphatase (NAP) were investigated in blood and/or smear samples from 18 women aged 23-46 years (mean 32.5 years) with trisomy 21 fetuses (17-21 weeks) and 28 women aged 20-42 years (mean 31 years) with normal fetuses (17-22 weeks). Immunochemical NAP investigations were carried out in 8 pathological and 8 normal pregnancies; cytochemical and immunocytochemical procedures were carried out in 18 pregnant women with trisomy 21 fetuses and 28 controls. NAP from women with trisomy 21 fetuses is characterized by: (1) a significant decrease in reactivity with anti-liver-type alkaline phosphatase (AP) and anti-NAP antisera; (2) low or very slight reactivity with antiplacental or anti-intestinal antibodies; (3) marked dispersion of NAP lead citrate reaction products or anti-NAP antibody colloidal gold-labelling in neutrophil cytoplasms, as detected by electron microscopy. This subcellular AP distribution (extramembranous) is different from that of normal NAP sites associated with plasma membrane, nuclear membrane and secretory vesicles. The NAP immunochemical and cytochemical characteristics suggest that neutrophils of a woman with a trisomy 21 fetus contain two AP isoenzymes: the liver/bone type and an atypical AP.

A comparative study of karyotypes, hematological variables and neutrophil alkaline phosphatase (NAP) was performed in 106 parents (53 couples) of children with free, homogeneous trisomy 21 and of 220

Neutrophil alkaline phosphatase (NAP) was analysed in 25 pregnant women with trisomy 21 foetuses whose chromosomal aberration was recognized by cytogenetic study after amniocentesis. Enzyme investigation was performed at 20-22 weeks of gestation using cytochemical and biochemical techniques. Twenty-nine women at the same stage of normal pregnancies were selected as controls. In parallel, each mother was karyotyped. Ten subjects from each series underwent biochemical and immunological investigation: measurement of enzyme levels, thermostability study and immunological tests with alkaline phosphatase isoenzyme antibodies. NAP from pregnant women with trisomy 21 foetuses was characterized by: (1) a lower rate of enzyme activity, (2) a large amount of heat-stable enzyme (T = 56 degrees C for biochemical assays, T = 85 degrees C for cytochemical tests), and (3) a marked loss of liver antigenicity. These findings suggest the presence in trisomy 21 pregnancies of a non-specific alkaline phosphatase isoenzyme which appears as an "enzyme marker" in maternal circulating neutrophils.

A study of karyotypes and neutrophil alkaline phosphatase (NAP) was carried out for 66 parents (33 couples) of trisomy 21 children and for 60 control parents (30 couples). Enzyme activity was determined simultaneously by biochemical and cytochemical techniques. In the mothers of trisomy 21 children we found: (a) by biochemical techniques, a significant increase of NAP activity in polymorphonuclear leukocyte (PMN) homogenates (P less than 0.01) and a lower supernatant/pellet ratio (P less than 0.01); (b) by cytochemical techniques (with or without thermal and urea treatments) NAP activity was significantly higher (P less than 0.001) than in control mothers; in the fathers, the two techniques gave normal NAP activity results.

The authors report an observation of a child with both trisomy 12(pter----q12) and monosomy 21(pter----q21). It is thus possible to detect the clinical signs which can be attributed to trisomy 12p and to monosomy 21ql respectively. The authors point out the originality of the maternal translocation which differs from the translocations affecting these two chromosomes previously described in the literature. Finally, the rarity of the type of adjacent-2 segregation is shown, and discussed according to the literature already published.

Two unrelated patients with partial trisomy 10p due to a paternal balanced translocation are reported. Though the sizes of the trisomic segment are not identical, both patients show: severe growth retardation, important psychomotor retardation and a dysmorphic mouth recalling a "tortois mouth". These observations are compared to twelve others from the literature.

A new case of partial trisomy 13 through unbalanced de novo translocation t(X;13) is reported. In situ hybridization has been used to specify breakage points on the X chromosome. This case is cytogenetically comparable with another reported case; the phenotypical aspect of these two patients is however different. This discrepancy is discussed.

Neutrophil alkaline phosphatase (NAP) from 12 mothers of normal children was investigated and the results compared to those of 7 mothers with trisomy 21 offsprings, in an attempt to determine a parental molecular change in this chromosomal abnormality. The biochemical properties of the enzyme were analyzed by the procedures of isoenzyme characterization, i.e. enzyme assays, thermostability, inhibition patterns and slab gel electrophoresis. Immunological properties were determined on 5 samples from normal mothers and on the same sample number of mothers with affected children. In these latter NAP showed characteristics that were to some extent different from the ones of normal controls. The following changes were observed: highly significant loading of membrane and nucleus pellets in NAP activity, poor effect of inhibitors on thermostable component and immunodepletion measured by a significant decrease of the normal affinity for antiliver and antiplacental alkaline phosphatase antisera. These findings are discussed in the light of our knowledge of alkaline phosphatase isoenzymes.

In order to give a genetic counsel to the mother and the two twin-sisters of an Hemophilia A boy, a familial investigation has been carried out. The study with the restriction fragment length polymorphism probes together with the hemostasis screening enabled to specify the status of each member of the family with respect to hemophilia A gene. This investigation evidenced the presence of two maternal alleles and one paternal allele in one of the twin-sisters. This led us to assume that she had a chromosomal abnormality in spite of her normal phenotype. The 47, XX, +(X) result of her karyotype confirmed this assumption. Therefore an accurate genetic counsel was provided to the members of this family and more particularly to the triple X subject.