Ataxic gait and mental retardation with absence of the paternal chromosome 8 and an idic(8)(p23.3): imprinting effect or nullisomy for distal 8p genes?

A female child with mild dysmorphisms, motor and mental retardation had a 45,XX,-8,-8,+psu dic(8)(p23.3) karyotype in blood lymphocytes, skin fibroblasts and in a lymphoblastoid cell line. DNA analysis showed that the proposita was nullisomic for the 8pter region distal to D8S264, at less than 1 cM from the telomere. Analysis of DNA polymorphisms of 38 loci spread along the entire chromosome 8 revealed that only maternal alleles were present, distributed in four heterozygous and four homozygous regions. This finding indicated that the rearrangement occurred during maternal meiosis in a chromosome recombinant with a minimum of seven crossovers. To our knowledge this is the first case of uniparental maternal disomy for chromosome 8 and of nullisomy for the distal 1-cM portion of the short arm. The available data are in favour of the assumption that no imprinted genes are present on chromosome 8. Thus, dysmorphisms, motor and mental retardation of the proposita are likely to be caused by the nullisomy for the region distal to D8S264, a region in which a recessive gene for epilepsy with progressive mental retardation is known to be located.

An analysis of Xq deletions.

We characterized by fluorescence in situ hybridization and Southern blotting 14 partial Xq monosomies, 11 due to terminal deletions and 3 secondary to X/autosome translocations. Three cases were mosaics with a XO cell line. In view of the possible role played by telomeres in chromosome segregation, we hypothesize a relationship between the loss of telomeric sequences in terminal deletions and the presence of 45,X cells. A correlation between phenotype and extent of deletion reveal that there is no correspondence between the size of the deletion and impairment of gonadal function. Turner stigmata are absent in patients without an XO cell line, when the breakpoint is distal to Xq24. A low birthweight is present whenever the breakpoint is at q22 or more proximal.

D8S7 is consistently deleted in inverted duplications of the short arm of chromosome 8 (inv dup 8p).

Ten patients with inverted duplication of 8p (inv dup 8p) were studied with cytogenetic, biochemical and molecular techniques. The duplication for the region 8p12-p22 was always associated with a deletion of the locus D8S7 (mapped in 8p23.1) as demonstrated with the probe pSW50 by both in situ hybridization and Southern blot. Restriction fragment length polymorphisms detected by probes pSW50 (1 case) and by pG2LPL35 (locus LPL) (two cases) were informative as to a maternal origin of the anomaly. The activity of glutathione reductase, whose gene maps in the duplicated region at 8p21.1, was increased in all patients. The recognizable phenotype of inv dup 8p includes neonatal hypotonia, prominent forehead, large mouth with everted lower lip, abnormally shaped large ears, brain malformations and severe mental retardation. Our findings indicate that the chromosome rearrangement is homogeneous at least for the presence of the deletion and support the hypothesis of a common mechanism of origin.

Thiamin balance in the gastrointestinal tract of sheep.

Six 5- to 6-month-old sheep fitted with rumen fistulas and reentrant cannulas in the duodenum and in the ileum were adapted to two dies low in thiamin and containing different percentages of urea nitrogen. The sheep were subjected to seven thiamin balance experiments, with continuous feeding and total collection of duodenal and ideal contents and feces for periods of 6 day each. Thiamin and dry matter were determined in aliquots of collected digesta and feces. Daily thiamin intake was always less than .3 mg, but average daily flow of thiamin into the duodenum was between 1.53 and 3.46 milligrams. Microbial net synthesis of thiamin in the forestomach system was between 1.44 and 3.23 mg/day, so 90 to 96% of thiamin entering the duodenum was of microbial origin. Disappearance of thiamin from the small intestines approximately equaled thiamin net synthesis in the forestomachs, indicating high absorption of microbially produced thiamin. In five experiments, thiamin balance in the large intestines was positive, but no measurements were made of thiamin breakdown within, and absorption from, the large intestines.

Glucocorticoid levels in blood plasma of normal and preketotic cows.

Twenty pregnant cows were kept in two feeding groups. Feeding regimens were designed to induce high milk production (16 kg milk/day) in group I and low production (2 kg/day) in group II. Milk weights were corrected for fat content. After onset of lactation, each cow was fed according to actual production level. Four cows from group I and two from group II developed clinical ketosis during the first few weeks of lactation. Blood taken weekly from all animals from about 2 weeks before until an average of 7 weeks after parturition was assayed for glucocorticoids, glucose and ketone bodies. Average plasma cortisol concentration for both groups was 4.5 +/- 2.6 ng/ml (range from 0 to 13 ng/ml). Plasma cortisol levels in cows which later developed clinical ketosis were not different from those in cows that remained healthy. There was, however, a positive correlation between blood glucose and plasma cortisol, and a negative correlation between blood ketone bodies and plasma cortisol. The findings suggest that adrenal cortical activity is interrelated with onset of ketosis although plasma cortisol levels appear unsuitable for identifying ketotic cows prior to clinical manifestation of the disorder.