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Emery-Dreifuss muscular dystrophy (EDMD) is characterized by slowly progressive muscle wasting and weakness; early contractures of the elbows, Achilles tendons, and spine; and cardiomyopathy associated with cardiac conduction defects. Clinically indistinguishable X-linked and autosomal forms of EDMD have been described. Mutations in the STA gene, encoding the nuclear envelope protein emerin, are responsible for X-linked EDMD, while mutations in the LMNA gene encoding lamins A and C by alternative splicing have been found in patients with autosomal dominant, autosomal recessive, and sporadic forms of EDMD. We report mutations in LMNA found in four familial and seven sporadic cases of EDMD, including seven novel mutations. Nine missense mutations and two small in-frame deletions were detected distributed throughout the gene. Most mutations (7/11) were detected within the LMNA exons encoding the central rod domain common to both lamins A/C. All of these missense mutations alter residues in the lamin A/C proteins conserved throughout evolution, implying an essential structural and/or functional role of these residues. One severely affected patient possesed two mutations, one specific to lamin A that may modify the phenotype of this patient. Mutations in LMNA were frequently identified among patients with sporadic and familial forms of EDMD. Further studies are needed to identify the factors modifying disease phenotype among patients harboring mutations within lamin A/C and to determine the effect of various mutations on lamin A/C structure and function.

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Since the Pap test was introduced in the 1940s, there has been an approximately 70% reduction in the incidence of squamous cell cervical cancers in many developed countries by the application of organized and opportunistic screening programs. The efficacy of the Pap test, however, is hampered by high interobserver variability and high false-negative and false-positive rates. The use of biomarkers has demonstrated the ability to overcome these issues, leading to improved positive predictive value of cervical screening results. In addition, the introduction of HPV primary screening programs will necessitate the use of a follow-up test with high specificity to triage the high number of HPV-positive tests. This paper will focus on protein biomarkers currently available for use in cervical cancer screening, which appear to improve the detection of women at greatest risk for developing cervical cancer, including Ki-67, p16INK4a, BD ProEx C, and Cytoactiv HPV L1.

We identified 10 solid organ transplant recipients with a histologic diagnosis of graft-vs-host disease (GVHD). Histologic slides were reviewed, and information on the transplant, HLA match, and blood product transfusion history was obtained. Molecular testing to evaluate the presence of donor lymphocytes (chimerism) was done in 1 case. All patients underwent at least 1 gastrointestinal biopsy; 1 patient also underwent a skin biopsy and 1 patient a liver biopsy; all specimens showed grade I to IV acute GVHD. Six patients had a diagnosis of GVHD within 3 months of blood product transfusion and/or solid organ transplantation, which is the time frame in which GVHD reportedly occurs after solid organ transplantation; 4 patients had a distant history of blood product transfusion or solid organ transplantation. In 1 patient, a molecular technique using the polymorphic marker DIS80 documented donor lymphocytes in the colonic tissue and blood (chimerism). Although histologic findings of GVHD are quite specific, they are not pathognomonic. A GVHD-like histologic pattern can be seen in other conditions such as drug reactions and viral infections. Demonstration of donor lymphocytes in the involved organ helps support the diagnosis of GVHD in questionable cases.

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Background Methionine synthase reductase (MTRR) catalyzes the regeneration of methylcobalamin, a cofactor of methionine synthase, an enzyme essential for maintaining adequate intracellular pools of methionine and tetrahydrofolate, as well as for maintaining homocysteine concentrations at nontoxic levels. We recently identified a common A -+ G polymorphism at position 66 of the eDNA sequence of MTRR; this variant was associated with a greater than normal risk for spina bifida in the presence of low levels of cobalamin.Objective To investigate whether the polymorphism was associated with alterations in levels of homocysteine, folate, and vitamin 8 1 ,and with risk of developing premature coronary artery disease~CAD), in a population of individuals presenting for cardiac catheterization procedures.Methods We screened 180 individuals aged < 58 years with angiographically documented coronary-artery occlusions or occlusion-free major arteries for the presence of the 66A -+ G MTRR polymorphism using a polymerase-chainreaction-based assay.Results We identified a trend in risk of premature CAD across the genotype groups (P=0.03) with a sex-adjusted relative risk of premature CAD equal to 1.49 (95% confidence interval 1.10-2.03) for the GG versus AA genotype groups. There was no difference in fasting levels of plasma total homocysteine, serum folate, and vitamin 8 12 among the three MTRR genotypes.Conclusions Our findings suggest that the GG genotype of MTRR is a significant risk factor for the development of premature CAD, by a mechanism independent of the detrimental vascular effects of hyperhomocysteinemia. This association needs to be confirmed in other studies. J

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