Fragile X syndrome and deletions in FMR1: new case and review of the literature.

The fragile X syndrome phenotype of mental retardation is almost always caused by abnormal CGG trinucleotide amplification within the FMR1 gene. Occasionally fragile X syndrome results from point mutations or deletions within or around the FMR1 locus. We have identified a mentally retarded African American male with typical fragile X phenotype and a 300-400 base pair intragenic deletion near the CGG repeat segment, present in his peripheral blood lymphocytes with no apparent mosaicism. His mother, who is not retarded, has a full FMR1 CGG expansion mutation with 700-900 repeats. A review of 23 published cases with FMR1 gene deletions shows full FMR1 mutation in the mother of only 1 other propositus, a male with FMR1 full mutation/premutation/deletion mosaicism of his cultured skin fibroblasts and peripheral blood lymphocytes. The various deletions within FMR1 and their clinical significance are reviewed.

A new X linked recessive syndrome of mental retardation and mild dysmorphism maps to Xq28.

Efforts to understand the genetic basis of mental retardation are greatly assisted by the identification of families with multiple relatives with mental retardation that clinical geneticists encounter in the routine practice of their profession. Here we describe a linkage study of a four generation family in which X linked recessive mental retardation (XLMR) is associated with minor dysmorphism and premature death of the affected males. Microsatellite based polymorphic loci evenly spaced over the entire X chromosome were used initially to detect linkage to Xq28. Further analysis identified a haplotype of Xq28 markers bounded proximally by locus DXS1113 and distally by DXS1108 that cosegregated with XLMR in this family. Two point lod scores > 3.0 provided strong evidence that the gene locus responsible for XLMR in this family is within this 7 Mb region of Xq28. The minor anomalies noted in some affected males were not distinctive enough to suggest a unique syndrome. None of our patients had features of the Waisman-Laxova syndrome or the PPM-X syndrome. The possibility of allelism with any of the five other non-specific XLMR syndromes (MRX3, MRX16, MRX25, MRX28, and MRX41) mapped to Xq28 could not be excluded. While the recognition of a gene responsible for this disorder needs much additional work, multiple female relatives at risk in this family benefit immediately from knowing their genotype and heterozygotes will have the opportunity to undergo prenatal diagnosis.

Development of monoclonal antibodies that identify Vibrio species commonly isolated from infections of humans, fish, and shellfish.

Monoclonal antibodies (MAbs) against Vibrio species that infect humans, fish, and shellfish were developed for application in rapid identifications. The pathogens included Vibrio alginolyticus, V. anguillarum, V. carchariae, V. cholerae, V. damsela, V. furnissii, V. harveyi, V. ordalii, V. parahaemolyticus, and V. vulnificus. Three types of MAbs were selected. The first important group included MAbs that reacted with only a single species. A second group comprised a number of MAbs that reacted with two, taxonomically closely related Vibrio species. For example, of 22 MAbs raised against V. alginolyticus, 6 recognized a 52-kDa flagellar H antigen common to both V. alginolyticus and V. parahaemolyticus; V. anguillarum and V. ordalii also shared antigens. A third group included three genus-specific MAbs that reacted with almost all Vibrio species but did not react with other members of the family Vibrionaceae (e.g., members of the Aeromonas, Photobacterium, and Plesiomonas genera) or a wide range of gram-negative bacteria representing many genera. This last group indicated the possible existence of an antigenic determinant common to Vibrio species. Two of these three genus-specific MAbs reacted with heat-stable antigenic determinants of Vibrio species as well as lipopolysaccharide extracted from Vibrio species. The use of the MAbs in blind tests and diagnosis of clinical isolates indicated that three different types of bacteria, viz., live, formalin-fixed, and sodium azide-killed bacteria, were detected consistently. Overall, it was found that the genus-specific MAbs were very useful for rapidly identifying vibrios in the screening of acute infections, while the species-specific MAbs and others were useful for completing the diagnosis.

Effect of diet on gentamicin-induced nephrotoxicosis in horses.

Gentamicin sulfate-induced nephrotoxicosis was compared in 2 groups of horses fed different rations. Four horses were fed only alfalfa hay, and 4 other horses were fed only whole oats. Seven days after initiation of the diet, all horses were given gentamicin IV (5 mg/kg of body weight) every 12 hours for 22 days. Urinary gamma-glutamyl-transferase to urinary creatinine (UGGT:UCr) ratio was calculated daily, and serum concentration of gentamicin was measured at 1 and 12 hours after drug administration. Results indicated that horses fed oats had greater renal tubular damage than did horses fed alfalfa. Mean UGGT:UCr for horses fed alfalfa was 47.1 +/- 18.8 and was 100.0 +/- 19.0 for horses fed oats (P = 0.007). The UGGT:UCr in horses fed oats was greater than 100 for a total of 54 days; horses fed alfalfa had UGGT:UCr greater than 100 for only 7 days. Two horses not given gentamicin were fed only oats and 2 were fed only alfalfa. These horses had mean UGGT:UCr of 17.6 +/- 2.2 and 30.5 +/- 3.0, respectively. Mean peak and trough concentrations of gentamicin were statistically different for horses fed oats and those fed alfalfa (peak 23.16 +/- 1.87 and 14.07 +/- 1.79 micrograms/ml, respectively [P = 0.0001], and trough, 1.81 +/- 0.69 and 0.71 +/- 0.70 micrograms/ml, respectively [P = 0.0270]). Mean half-lives of gentamicin (estimated from peak and trough concentrations) for horses fed alfalfa (2.58 +/- 0.26 hours) and horses fed oats (2.88 +/- 0.27 hours) were not significantly different. Horses fed only oats had greater degree of gentamicin-induced nephrotoxicosis than did those fed only alfalfa.

Effects of diet and feeding on postprandial serum gastrin and insulin concentration in adult horses.

Gastrin is the only hormone known to stimulate secretion of hydrochloric acid. It also has trophic effects on specific parts of the mucosa of the gastrointestinal tract. Using radioimmunoassay techniques, postprandial serum gastrin and insulin concentrations were measured in six adult horses to establish effects of different diets on gastrin concentrations. Insulin concentrations were measured to provide support to the patterns of gastrin secretion because patterns of insulin secretion were already known. The horses were fed coastal bermuda hay, or twice daily 5 kg of a complete pelleted ration, 5 kg of commercial sweet feed or 5 kg of the sweet feed together with hay. There was little change in serum gastrin or insulin concentrations after feeding hay alone. Rations containing more readily available nutrients (pellets, sweet feed) produced significant increases in postprandial serum gastrin and insulin concentrations. Gastrin concentrations also varied according to the duration of feeding each diet, but this was not seen with insulin. These results indicated that gastrin secretion, and therefore possibly gastric acid secretion, were markedly influenced by dietary composition and duration of feeding a diet. There appeared to be some adaptation of the stomach (gastrin secretion) to changes in diet, but this was not accompanied by indications of adaptation in the endocrine pancreas (insulin secretion).

Disseminated intravascular coagulation in experimental intestinal strangulation obstruction in ponies.

Total strangulation obstruction of the caudal part of the jejunum was induced in 3 groups (each of 3 ponies) for 2, 4, and 6 hours. Coagulation tests which included blood platelet counts, prothrombin time, activated partial thromboplastin time, activated coagulation time, plasma fibrinogen level, and fibrin/fibrinogen degradation products assay were performed at specified time intervals for 1 week or until death of the experimental ponies. Another 3 ponies (sham-operated) were similarly treated, except that intestinal strangulation obstruction (ISO) was not induced. Necropsy was done on ponies that were euthanatized 9 days after the sampling period and on 2 ponies that died. Six hours of ISO resulted in severe ischemic damage to the intestines, characterized by hemorrhagic infarction, with or without perforation, in ponies that died, and total loss of mucosa with moderate to severe fibrosis of the intestinal wall in the surviving pony of this group. This damage was associated with significant coagulopathies, notably prolonged prothrombin time and activated partial thromboplastin time, decreased blood platelets count, and the presence of high levels of fibrin/fibrinogen degradation products (40 micrograms/ml). These laboratory findings are indicative of disseminated intravascular coagulation. In contrast, the jejunal segments of the ponies subjected to 2 and 4 hours of ISO were viable as revealed by histopathologic examination. There were no significant changes found in their coagulation profiles.(ABSTRACT TRUNCATED AT 250 WORDS)