Platelet-associated IgG, IgM, and C3 in paediatric infectious disease

Elevated amounts of platelet-associated serum proteins (PASP) can be detected in idiopathic thrombocytopenic purpura (ITP) and are considered to be of patho-aetiological importance especially in the case of acute ITP, that commonly follows acute febrile illnesses. Using a micro-enzyme-linked immunoassay we examined PASP (IgG, IgM, and C3) in 120 paediatric patients with acute fever caused by viral (n = 45), bacterial (n = 48), or non-detectable agents (n = 27) and compared those values to the levels of PASP of an own paediatric control group (n = 21). Two of the patients presented mild temporary thrombocytopenia without clinical signs in the course of their infectious disease. While having normal platelet counts, the majority of our patients (69.2%) however, showed increased levels of PASP (IgG, IgM, C3; single or combined). Significant differences of PASP levels by discrimination of viral and bacterial diseases could not be demonstrated. Elevated platelet-associated complement was of special interest, because - in the absence of low platelet counts due to platelet-specific antibodies - it must be regarded as an indicator for immune complexes (IC) binding to thrombocyte surface IgG Fc-receptors. Thus we suggest that platelets play a considerable role in the elimination of circulating IC.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Mesomelic and rhizomelic short stature: The phenotype of combined Leri-Weill dyschondrosteosis and achondroplasia or hypochondroplasia

We studied two children with combined genetic skeletal disorders. Both had Leri-Weill dyschondrosteosis (LWD); one also had achondroplasia and the other had hypochondroplasia. Both had severe short stature and evidence of rhizomelia and mesomelia as well as other phenotypic features of their individual genetic disorders. Achondroplasia was due to the G380R FGF3R mutation and hypochondroplasia to a N540K mutation in the same gene. The patient with hypochondroplasia had a heterozygous SHOX deletion; no SHOX mutation was identified in the child with achondroplasia. The phenotypes of combined LWD and achondroplasia or hypochondroplasia appeared to be less than additive, suggesting that SHOX and FGFR3 act on overlapping pathways of bone growth and development.