PubMed Health⌕ Search

Biomedical subjects

J Stajich

Publications and source records attributed to J Stajich.

10 recordsLinked to original sources
PubMed1992

Linkage studies in Charcot-Marie-Tooth disease type 2: evidence that CMT types 1 and 2 are distinct genetic entities.

Charcot-Marie-Tooth disease (CMT), the most common inherited peripheral neuropathy, is a progressive sensorimotor neuropathy divided into types 1 and 2 based upon electrophysiologic and neuropathologic differences. The more common autosomal dominant form of CMT type 1 (hereditary motor and sensory neuropathy type I) is genetically heterogeneous, with genes located on chromosomes 1 (type 1B) or 17 (type 1A). However, no locus for CMT type 2 is known. We have performed linkage studies on three large multigenerational CMT type 2 families using probes from chromosome 1 and chromosome 17, which span their respective linkage regions. Multipoint analysis of the chromosome 17 markers excluded linkage over an area of 45 cM--15 cM proximal and 30 cM distal to the region containing CMT type 1A. Multipoint analysis of the chromosome 1 markers exclude linkage 15 cM proximal and 20 cM distal to FC-gamma-RII in the region of CMT 1B. These data indicate that CMT type 2 is genetically distinct from CMT type 1.

Adolescent↗
PubMed1990

Tight linkage of creatine kinase (CKMM) to myotonic dystrophy on chromosome 19.

The myotonic dystrophy (DM) gene is localized to the proximal long arm of chromosome 19. There have been reports of tight linkage to a number of chromosome 19 markers, including APOC2 and creatine kinase muscle type (CKMM), but they did not establish orientation of the 2 markers to DM. We screened several large multi-generational DM families for linkage to a series of chromosome 19 markers including CKMM. CKMM is tightly linked to DM in these data with z(theta) = 28.41; theta = 0.01. Analysis of cross-over data indicates CKMM is on the same side and closer to DM than APOC2. Thus, CKMM is a useful probe for carrier detection studies in presymptomatic individuals as well as for prenatal diagnosis.

Chromosome Mapping↗
PubMed1989

Linkage of Charcot-Marie-Tooth neuropathy type 1a to chromosome 17.

Charcot-Marie-Tooth disease Type 1 (CMT) is an inherited neuropathy with known genetic heterogeneity, with at least one autosomal dominant form (CMT Type 1b) linked to the Duffy region of chromosome 1. Autosomal dominant families not demonstrating linkage to the Duffy blood group marker have been designated CMT Type 1a. We report linkage of six CMT Type 1a families to the chromosome 17 markers EW301 (D17S58) and pA10-41 (D17S71) with maximum LOD scores of zeta = 10.49 at theta (maximum recombination fraction) = 0.05 and zeta = 7.36 at theta = 0.06, respectively.

Charcot-Marie-Tooth Disease↗
PubMed1988

Systematic gene mapping in man: data management considerations.

The application of recombinant DNA technology to linkage analysis is revolutionizing the gene mapping field through the availability of an increasing number of restriction fragment length polymorphisms (RFLP). The successful mapping of the human genome will lead to a new era of research in human genetics with implications for carrier detection and prenatal diagnosis in any number of disorders. In addition, the development of RFLP tightly linked to a disease is critical for the potential identification of the genetic defect. A systematic approach to human gene mapping whereby it is possible to simultaneously screen several disorders for linkage is discussed. Guidelines for the database management, field studies, DNA and lymphoblast cell transformation, family history and laboratory data are included. This methodology represents the integration and application of statistical and molecular genetic, clinical and tissue culture expertise to human gene mapping.

Chromosome Aberrations↗
PubMed1985

Cardiac involvement in myotonic muscular dystrophy.

Cardiac illness in myotonic muscular dystrophy (MyD) is infrequent, but subclinical cardiac involvement in MyD is very common (found in 42 of 46 subjects) and may be responsible for sudden death. In this series, we found ECG abnormalities in 72%, left ventricular dysfunction in 70%, mitral valve prolapse in 37%, and sudden death in 4%. Four deaths during the study period were due to acute left ventricular failure, one to sepsis and respiratory insufficiency, and one was unexplained. We did not find ominous bradyarrhythmias or atrioventricular block, evidence of congestive heart failure, noninvasive evidence of coronary artery disease, or any correlation of type or amount of cardiac involvement with any clinical parameter such as age, sex, or severity of systemic dystrophy. We feel tachyarrhythmias may play as important a role in sudden death of myotonic muscular dystrophy subjects as bradyarrhythmias, and coronary artery disease in addition to cardiac dystrophy may produce arrhythmias and myocardial dysfunction in myotonic muscular dystrophy. In addition, some subjects have an unusual form of resting left ventricular dysfunction which improves with exercise. The most important problem in the clinical management of myotonic muscular dystrophy subjects is sudden death, and the solution does not appear to be empiric ventricular pacing. Our recommendations for prophylaxis of sudden death in myotonic muscular dystrophy are noninvasive investigation of coronary artery disease in subjects with significant risk factors, with angiography and surgery if indicated: detailed evaluation of syncopal and presyncopal events, including electrophysiologic testing, with pacemaker or antiarrhythmic drug therapy if indicated; and consideration of ventricular pacing of asymptomatic subjects if severe bradycardia or marked intraventricular conduction delay develops during follow-up, serial 12-lead ECGs. The documentation of tachyarrhythmias during sudden death and syncopal episodes in myotonic muscular dystrophy subjects makes ventricular pacing alone an uncertain modality for prevention of sudden death in subjects with only mildly lengthened PR or QRS intervals, and suggests a combination of pacemaker and antiarrhythmic drug therapy for the myotonic muscular dystrophy subject with syncope of no apparent cause.

Adult↗
PubMed1983

Recombinant DNA strategies in genetic neurological diseases.

The application of recombinant DNA techniques applied to the study of genetic neurological diseases will play a major role in the practice of neurology in upcoming years. Strategies are now available to develop useful and relatively simple biochemical diagnostic tests for heterozygous individuals with diseases inherited as autosomal dominant traits. In addition, molecular genetic methods will lead to the delineation of the genomic mutations responsible for these diseases. This review will update the current status of research in several neurological genetic diseases including myotonic muscular dystrophy, Huntington's disease, Charcot-Marie-Tooth disease and Duchenne muscular dystrophy (X-linked). An introduction and overview of the methodology is provided. Specific research strategies including random screening of libraries, chromosome walking, messenger RNA selection, and messenger RNA translation are described. These strategies are designed to provide heterozygote identification, prenatal diagnosis and gestational management, the development of rational therapies, and the understanding of the molecular basis of disease expression.

Charcot-Marie-Tooth Disease↗