Contribution of molecular biology to the diagnosis of monogenic hereditary nephropathies

Schematically, gene identification can be achieved by functional cloning, based on preexisting knowledge about the basic biochemical defect, positional cloning, initiated by the mapping of the responsible gene to its correct location on a chromosome, or by a combination of these two approaches called "candidate gene" approach. Genes of numerous monogenic hereditary renal disorders have been identified during the last few years by one of these approaches, particularly, the PKD1 and PKD2 genes involved in autosomal dominant polycystic kidney disease, as well as the genes encoding different type IV collagen alpha chains, responsible for Alport syndrome. This allows novel insights in the understanding of the pathogenesis of hereditary renal diseases and has opened new areas of genetic diagnosis.     

The welfare of children and "the new federalism."

Discusses some concerns of members of the National Governors' Association about "new federalism" proposals offered by the Reagan administration (e.g., a turnback of many programs affecting children, youth, and families, and the revenue sources to support them, from the federal government to the states). The impact of new federalism proposals is analyzed in relation to target populations to be affected by the proposed changes. (3 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Emperor's New Clothes syndrome. Description of a new epidemic

In 1971, F. Gross, inspired by "The Emperor's new clothes" (H.C. Andersen--1835), published in the New England Journal of Medicine, a report of an endemic polysystem disease: the emperor's clothes syndrome. In the first place, it touches students or physicians who fear losing their prestige. From personal observations, we describe a new epidemic of this disease whose radiological image is the main vector. By this comment, we wish to attract the attention to the danger of giving a diagnosis uniquely on the basis of the complementary examinations. We want to underline the importance of the medical history and physical examination. All clinical or radiological data, all biological phenomenons are subject to variable interpretation. There exist statistical methods to estimate the sensitivity, the specificity and the clinical value of a test.     

Reply to Silverman's "Defense of simplicity."

Replies to criticisms of autoinstructional techniques previously described by K. R. Stafford and C. F. Combs (1967) and discusses these techniques in terms of stimulus–response models. (0 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A reply to Golland's "Politics of Leveling."

In "Psychoanalysis and Psychoanalytic therapy: Is There a Meaningful Distinction in the Process?" J. L. Fosshage (see record 1997-38544-006) reassessed, on the basis of theory, research, and practice, the extrinsic and intrinsic criteria for psychoanalysis and concluded, from today's perspective, that a meaningful distinction with psychoanalytic psychotherapy cannot be made. J. H. Golland (see record 1999-00333-007) coming from a classical psychoanalytic perspective, decried these conclusions about psychoanalysis and psychoanalytic psychotherapy. This article is a reply to Golland. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enzymatic and molecular diagnosis of Gaucher disease

Advances in the knowledge of the molecular genetics of Gaucher disease has made diagnosis more certain. Carrier detection in kindreds in which the responsible mutation has been defined is completely reliable now. Coupled with enzymatic assays, the diagnostic capabilities are greater than before. Use of these methods provides important information to individuals at risk and allows them to make critical decisions. The new, simplified methods reviewed in this article permit the molecular diagnosis of the disease and carrier stage of large numbers of samples within 1 week.     

Prenatal ultrasonographic and molecular diagnosis of Apert syndrome

Apert syndrome is a rare craniosynostosis syndrome with significant bilateral syndactyly of the hands and feet. Usually it is detected by ultrasonography during the third trimester unless there is a family history. We present an interesting sporadic case with features consistent with Apert syndrome detected as early as the first trimester. A first-trimester ultrasound evaluation prior to chorionic villus sampling (CVS) for maternal age 41 was within normal limits except for the suggestion of a 'mitten-like' hand and proximally placed thumb. Mid-trimester ultrasound was not diagnostic; however, following the development of polyhydramnios in the third trimester, the evaluation of the digits and facial features were strongly suggestive of Apert syndrome. Amniocentesis was performed and a molecular diagnosis of Apert syndrome was made and confirmed on cord blood.     

A response to Sprott's "Use of chi square."

Issue is taken with Sprott's criticisms of the use of chi square in birth-order studies, including the author's recent paper on alcoholism, birth order, and family size. Sprott's argument that the chi-square test is inapproprite is discussed, but further statistical tests not involving chi square yielded the same conclusion, i.e, no birth-order effect. Also, interactions between birth-order effects and family sizes are unimportant for the alcoholism data and difficult to evaluate in any birth-order study where an overall test is required. The corrected family-size analyses are defended as the best available. Sprott's suggested changes in the family-size analyses do not affect the conclusion that persons from large families are over-represented among alcoholics. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Perspectives and molecular diagnosis of the fragile X syndrome

The fragile X syndrome is the most common mendelianly inherited form of mental retardation. The underlying mutation is usually a triplet repeat (CGG) that is variable in length and undergoes a tremendous length amplification in affected individuals. The mutation leads to absence expression of a gene, which apparently functions as an RNA binding protein. Molecular diagnostic testing for the mutation is conducted using direct genomic Southern blot analysis and polymerase chain reaction. Because the mutation is so common and a single type of mutation accounts for most individuals with the disease, widespread genetic screening can be considered.     

Current diagnosis: hereditary metabolic diseases of the liver (primary hemochromatosis, Wilson disease)

Primary hemochromatosis is characterized by a specific pattern of clinical manifestations. It includes liver disease with hepatomegaly, glucose intolerance, e.g. diabetes, hyperpigmentation oft the skin, impotence/ amenorrhea, arthropathy, cardiomyopathy and fatigue. Laboratory investigation reveals significantly elevated serum ferritin and transferrin saturation with iron. The diagnosis is confirmed by liver biopsy and quantitative determination of elevated liver iron content. Wilson's disease represents a copper storage disease. Prominent clinical features are hepatomegaly and splenomegaly. Neurological alterations and detection of Kayser-Fleischer corneal rings are typical. In the acute initial phase the often young patients present with Coombs-negative hemolysis. Psychiatric alterations, cardiomyopathy, arthropathy, nephropathy, as well as thrombocytopenia and leucopenia are other clinical features. Laboratory parameters of Wilson's disease include low serum ceruloplasmin and serum copper. There is an elevated urinary copper excretion and elevated serum free copper concentration. The diagnosis is confirmed by liver biopsy with quantitative determination of an elevated liver copper content.