Deletion including the oligophrenin-1 gene associated with enlarged cerebral ventricles, cerebellar hypoplasia, seizures and ataxia.

Non-specific X-linked mental retardation is a heterogeneous group of disorders with an incidence of approximately 1 in 500 males. A recently identified gene in Xq12, encoding a Rho-GTPase-activating protein, was found to be mutated in individuals with mental retardation. We describe here two sisters with a 46,XY karyotype and a microdeletion of the oligophrenin-1 gene and 1.1 Mb of flanking DNA. We have characterised the molecular interval defining this microdeletion syndrome with the fibre-FISH technique. A visual physical map of 1.2 Mb was constructed which spans the oligophrenin-1 gene and the androgen receptor gene. The analysis of the patients revealed a deletion which extended from the 5' end of the AR gene to a region approximately 80 kb proximal to the EPLG2 gene. The clinical manifestations of the two sisters include psychomotor retardation, seizures, ataxia, hypotonia and complete androgen insensitivity. Cranial MRI scans show enlargement of the cerebral ventricles and cerebellar hypoplasia. Our findings give further support for the involvement of the oligophrenin-1 gene in specific morphological abnormalities of the brain which is of importance in the investigation of male patients presenting with mental retardation. In combination with our results from physical mapping we suggest that a region around the oligophrenin-1 locus is relatively bereft of vital genes.

Social outcome of handicapped children as adults.

The social status of 52 disabled young adults (29 men, 23 women) was reviewed at the age of 19 to 25 years, and compared with that of 209 age-matched controls. 40 had successfully completed elementary school and 10 had completed high-school. 28 had gone on to basic further education and 11 had progressed to more advanced levels. 35 per cent of the study group and 11 per cent of the controls had had no further education. Half of the study group were receiving disability benefit and 12 had no occupation outside the home. There was little difference in present employment status between groups, but the study group had experienced twice as much unemployment as controls. Leaving the parents' home and sexual experience were delayed among the study group. The results indicate the need for more practical support for these adolescents and their parents.

Neonatal jaundice and fatty acid composition of the maternal diet.

The role of serum fatty acid composition in neonatal jaundice was studied by comparing the incidence of jaundice among 332 newborn infants receiving breast milk from mothers on a diet with either a low (0.1, n = 145) or a high (1.5, n = 187) polyunsaturated to saturated fatty acid (P/S) ratio. The diet was started immediately after delivery. The composition of fatty acids in the breast milk and sera of the mothers and in the sera of the newborns was evaluated from a random sample of 15 mother-newborn pairs on the control diet (low P/S ratio) and 19 pairs on the experimental diet. Five days after delivery the relative amounts of fatty acids, especially that of linoleate, in the sera of the mothers differed significantly depending on the diet. Differences were also observed in breast milk samples taken three, four or five days after delivery and in the sera of the newborns sampled at the age of four or five days. Nine of the 145 newborn infants (6.2%) in the control group had to be treated with light therapy compared with 12 out of 187 (6.4%) of the newborn infants in the experimental group (high P/S ratio). Serum bilirubin concentrations were 142.5 mumol/l (SD 65.8) and 140.7 mumol/l (SD 73.5) in the experimental and control groups, respectively, at the age of five days. It appears that the changes in the composition of serum fatty acids reached in this study had no effect on the neonatal jaundice.

Trisomy 10p produced by recombination involving complex paternal translocation between chromosomes 1 and 10.

A complex and unique, apparently balanced translocation involving No. 1 long arm and No. 10 short and long arm, segregated in a family and produced an unbalanced progeny with recombination of t(10) translocation chromosome during paternal meiosis.

The effect of oral thyrotropin-releasing hormone on thyroid function and the composition of breast milk in puerperal women.

To determine the effect of oral administration of thyrotropin-releasing hormone (TRH) on the thyroid function and on the composition of breast milk in the early puerperium, six lactating women were treated with a single dose of 40 mg of synthetic TRH and six women were treated with placebo. Serial serum samples taken before and between one and 25 hours after TRH administration were assayed with specific radioimmunoassays for thyrotropin (TSH), triiodothyronine (T3) and total thyroxine (T4). Milk samples were collected three times a day and their major fatty acids were determined by gas-liquid chromatography and were compared with those obtained from normal lactating women. A statistically significant TSH elevation was observed between one and six hours after TRH administration, with a peak value of 23.7 +/- 10.6 mU/liter at three hours. The T3 concentration rose between three and nine hours after TRH administration, with a peak of 6.3 +/- 1.2 nmole/liter at six hours. The T4 elevation was statistically significant between six and 12 hours after TRH administration. The fatty acid content of milk samples from women treated with TRH did not differ from the normal series. A single daily dose of oral TRH thus caused a temporary thyroid stimulation. It is doubtful whether this could lead to hyperthyroidism since the levels of thyroid hormones became normal within ten hours after TRH administration.