Mutational analysis of PHEX gene in X-linked hypophosphatemia

Hypophosphatemic rickets is commonly an X-linked dominant disorder (XLH or HYP) associated with a renal tubular defect in phosphate transport and bone deformities. The XLH gene, referred to as PHEX, or formerly as PEX (phosphate regulating gene with homologies to endopeptidases on the X-chromosome), encodes a 749-amino acid protein that putatively consists of an intracellular, transmembrane, and extracellular domain. PHEX mutations have been observed in XLH patients, and we have undertaken studies to characterize such mutations in 46 unrelated XLH kindreds and 22 unrelated patients with nonfamilial XLH by single stranded conformational polymorphism and DNA sequence analysis. We identified 31 mutations (7 nonsense, 6 deletions, 2 deletional insertions, 1 duplication, 2 insertions, 4 splice site, 8 missense, and 1 within the 5' untranslated region), of which 30 were scattered throughout the putative extracellular domain, together with 6 polymorphisms that had heterozygosity frequencies ranging from less than 1% to 43%. Single stranded conformational polymorphism was found to detect more than 60% of these mutations. Over 20% of the mutations were observed in nonfamilial XLH patients, who represented de novo occurrences of PHEX mutations. The unique point mutation (a-->g) of the 5'untranslated region together with the other mutations indicates that the dominant XLH phenotype is unlikely to be explained by haplo-insufficiency or a dominant negative effect.     

Diagnosis of uterine abnormalities with radionuclide imaging

A pelvic hypervascular blush often creates a diagnostic dilemma during radionuclide abdominal imaging studies in females. This blush is shown to be due to uterine vascularity that is more prominent in the secretory and menstrual phases of the menstrual cycle. Significant uterine vascularity in the earlier phases is inappropriate and may be pathologic. Three such cases are presented in which increased uterine vascularity on radionuclide imaging during the proliferative phase either lead to a diagnosis or supported a clinical finding.     

Ethylenediamine tetraacetic acid-associated leukoagglutination

Three cases of ethylenediamine tetraacetic acid (EDTA)-induced leukoagglutination noted on peripheral blood films are reported. Two cases of EDTA-induced agglutination of benign lymphocytes, and one case of EDTA-induced mature neutrophil satellitosis about immature neutrophil were observed. EDTA-induced agglutination of malignant lymphoid cells has been reported in blood films from patients with malignant lymphoma and chronic lymphocytic leukemia. Our two cases are the first reported instances of EDTA-induced agglutination of benign lymphocytes. EDTA-induced agglutination of neutrophils is a well recognized, but uncommon event. This case was unusual because mature neutrophils were rosetted about a central immature granulocyte and no agglutination of mature neutrophils was noted.