Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer's disease

The allelic frequency of the gene for the K variant of butyrylcholinesterase (BCHE-K) was 0.17 in 74 subjects with late-onset (age > 65 years) histopathologically diagnosed Alzheimer's disease (AD), which was higher than the frequencies in 104 elderly control subjects (0.09), in 14 early-onset cases of confirmed AD (0.07) and in 29 confirmed cases of other dementia (0.10). The association of BCHE-K with late-onset AD was limited to carriers of the epsilon 4 allele of the apolipoprotein E gene (APOE), among whom the presence of BCHE-K gave an odds ratio of confirmed late-onset AD of 6.9 (95% C.I. 1.65-29) in subjects > 65 years and of 12.8 (1.9-86) in subjects > 75 years. In APOE epsilon 4 carriers over 75 years, only 1/22 controls, compared with 10/24 confirmed late-onset AD cases, had BCHE-K. We suggest that BCHE-K, or a nearby gene on chromosome 3, acts in synergy with APOE epsilon 4 as a susceptibility gene for late-onset AD.      

ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome

It was shown recently that mutations of the ATRX gene give rise to a severe, X-linked form of syndromal mental retardation associated with alpha thalassaemia (ATR-X syndrome). In this study, we have characterised the full-length cDNA and predicted structure of the ATRX protein. Comparative analysis shows that it is an entirely new member of the SNF2 subgroup of a superfamily of proteins with similar ATPase and helicase domains. ATRX probably acts as a regulator of gene expression. Definition of its genomic structure enabled us to identify four novel splicing defects by screening 52 affected individuals. Correlation between these and previously identified mutations with variations in the ATR-X phenotype provides insights into the pathophysiology of this disease and the normal role of the ATRX protein in vivo.      

Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees

Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man. Characterization of mutations in the 21- hydroxylase gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase chain reaction (PCR). The most common mutation is conversion of an A or C at nt656 to a G in the second intron causing aberrant splicing of mRNA. Homozygosity for nt656G is associated with profoundly deficient adrenal cortisol and aldosterone synthesis, secondary hypersecretion of adrenal androgens, and a severe form of congenital adrenal hyperplasia (CAH) characterized by ambiguous genitalia and/or sodium wasting in newborns. During the course of genetic analysis of CYP21 mutations in CAH families, we and others have noticed a number of relatives genotyped as nt656G homozygotes, yet showing no clinical signs of disease. A number of lines of evidence have led us to propose that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one haplotype during PCR amplification of CYP21. For prenatal diagnosis, we recommend that microsatellite typing be used as a supplement to CYP21 genotyping in order to resolve ambiguities at nt656.      

Patterns of femoral head migration in osteoarthritis of the hip: a reappraisal with CT and pathologic correlation

Although medial, superior, and axial patterns of migration of the femoral head in osteoarthritis of the hip have been well described, it is not clear what anatomic and biomechanical factors determine the direction of migration. The authors studied 22 patients with bilateral (11 patients) or unilateral (11 patients) osteoarthritis by means of conventional radiography and computed tomography (CT) to define any relationships between migration in the coronal plane and that in the transverse plane and to determine whether femoral anteversion, acetabular anteversion, femoral neck-shaft angle, or acetabular inclination were related to particular migration patterns. Anterior migration was evident in 14 of the 19 hips with a superior migration pattern, whereas posterior migration was present in five of the seven hips with a medial migration pattern. In the remainder of cases, no migration in the transverse plane was present. Femoral anteversion as determined with CT, femoral neck-shaft angle, angle of acetabular inclination, and acetabular anteversion angle in this relatively small sample were all found to be within normal limits and appeared to have no influence on the occurrence of a specific pattern of femoral head migration.     

Urokinase in gastrointestinal tract bleeding

Selective urokinase infusion into the superior mesenteric artery allowed the accurate determination of the site of small bowel bleeding in a patient with recurrent lower gastrointestinal bleeding who bled despite resective surgery and who had negative findings on four angiograms. Fibrinolytic agents are useful in rare cases in which the need for successful and accurate diagnosis outweighs the risks of reactivating the bleeding.