It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.

kept at +4C0 for 4 8 hrs, for phagocytosis, candidacidal activity, chemotaxis and spont. & stim. NBT test (for methods see : Ital. J. Pediat. 4:571,1978). Phagocytosis, candidacidal activity and NBT test remained unchanged at 24 and 4 8 hrs (104% and loo%, 94% and 93%, 94% and 92% respectively of initial values). Chemotaxis only showed a slight decrease (98% and 73%). me present results show a satisfactory functional stability of PMN collected by leukafiltration, suggesting that the same concentrate may be effectively transfused for three consecutive days.

No abstract

Cerebrospinal fluid aminoacid analysis in a girl with severe psychomotor retardation, hypotonia, hyperreflexia and growth acceleration showed highly increased levels of free gamma-aminobutyric acid (4.8 mumol/l; range in twenty controls 0.04-0.12, median 0.08), homocarnosine, a dipeptide of gamma-aminobutyric acid and histidine (23.4 mumol/l; control range 4.0-8.7, median 7.6) and of beta-alanine, an alternative substrate for gamma-aminobutyric acid-transaminase (0.48 mumol/l; control range 0.02-0.06, median 0.05). Liver gamma-aminobutyric acid-transaminase activity was deficient (0.07 mumol/mg protein h; range in ten controls 0.31-0.69, median 0.38). Fasting plasma growth hormone levels were increased (7.9-38.4 ng/ml; nl less than 5). Brain evoked responses were suggestive of leukodystrophy. A brother of this patient, showing a similar clinical picture, had died at one year. Postmortem examination of his brain showed leukodystrophy of the type seen in amino acidopathies such as phenylketonuria. This appears to be the first report of gamma-aminobutyric acid-transaminase deficiency.

Dopamine is frequently used in neonatal intensive care for its vasopressor, renal vasodilating, and cardiac inotropic properties. The effect of i.v. dopamine infusion on neonatal pituitary hormone secretion is currently unknown. We observed strikingly low serum concentrations of growth hormone (GH) and prolactin (PRL) during a therapeutic, standardized, isovolumetric, partial exchange transfusion (blood sampling every 20 min for 6 h) in two polycythemic neonates requiring intensive therapy, including continuous dopamine infusion. In addition, the secretion of GH and PRL was studied in three neonates with symptomatic polycythemia (gestational age 34-38 wk; birth weight 2110-2530 g; postnatal age 10-30 h) during a partial exchange transfusion, including an intervening dopamine infusion (8 micrograms/kg/min i.v. for 2 h). The GH and PRL profiles were evaluated by deconvolution analysis. Initially, the three newborns exhibited high-amplitude, pulsatile GH secretion and continuously elevated PRL release. During the dopamine infusion, GH secretion was virtually abolished and PRL release was reduced by at least 50%. Dopamine withdrawal was associated with a rebound release of GH and PRL. Finally, serum GH and PRL concentrations were studied in nine nonpolycythemic newborns (gestational age 31-40 wk; birth weight 1680-4000 g; postnatal age 2-28 d) at the end of a prolonged dopamine infusion (3-5 micrograms/kg/min i.v. for 2-27 d). Within 2 h after dopamine withdrawal, GH and PRL levels increased a median 3-fold and 10-fold respectively. These data concord to indicate that dopamine is a potent inhibitor of GH and PRL secretion in the human newborn.