Search PubMed⌕ Search

Biomedical subjects

T Siddique

Publications and source records attributed to T Siddique.

At least 73 records · Page 4Linked to original sources
PubMed1989

Duchenne muscular dystrophy: detection of deletion carriers by spectrophotometric densitometry.

DNA isolated from a family segregating a deletion in the Duchenne muscular dystrophy gene and control families was digested with restriction enzymes, Southern transferred, and probed with a radioactive dystrophin cDNA probe. The resulting autoradiographs were analyzed with a densitometric spectrophotometer to detect carriers of the deletion. The carrier status of females in the deletion pedigree was independently determined by genomic probes and confirmed by densitometry. In many Duchenne families, deletions will only be observed using cDNA probes which show few restriction fragment length polymorphisms (RFLPs). Such deletions would normally have to be detected using dosage gels. The spectrophotometric densitometry technique used by us does not require dosage gels, and avoids problems arising from non-informative meioses and cross-overs. It should be possible to screen every family with an exon deletion by spectrophotometric densitometry provided the presently available cDNA is suitably reduced to produce fewer bands on autoradiographs.

Autoradiography↗
PubMed1989

An exclusion map for facioscapulohumeral (Landouzy-Déjérine) disease.

By using the genetic linkage data between the facioscapulohumeral muscular dystrophy (FSHD) gene and 57 markers on various autosomes, we have constructed an exclusion map for this disorder. The maximum likelihood location of the FSHD gene and the percentage of the excluded areas on each chromosome are presented here. This exclusion map shows that more than 80% of the genome has been excluded as a likely location of any locus responsible for FSHD in the majority of families. Chromosomes 3, 5, 10, 11, 15, and 19 remain largely unexcluded. Concentration on the highlighted areas of the genome should facilitate the identification of the site of the FSHD gene.

Chromosome Mapping↗
PubMed1989

Linkage analysis in the spinal muscular atrophy type of facioscapulohumeral disease.

Facioscapulohumeral disease is probably a heterogeneous disorder. We have ascertained and sampled two multigeneration families with the neurogenic form of this disorder, considered to be a type of spinal muscular atrophy (FSHSMA). The two families have 36 affected members. Linkage studies with 10 expressed and seven DNA restriction fragment length polymorphism (RFLP) markers failed to show significant linkage (Zmax greater than or equal to 3.00). However, two areas of probable linkage were defined on chromosomes 1p and 4q with the markers MNS (Zmax = 1.47 at theta max = 0.10) and PGM1 (Zmax = 0.94 at theta max = 0.001) respectively. We are using additional RFLPs from these and other areas of the human genome to screen these families for linkage to FSHSMA.

Chromosome Mapping↗
PubMed1989

Linkage analysis in familial amyotrophic lateral sclerosis.

Familial amyotrophic lateral sclerosis (FALS) constitutes 5 to 10% of cases of ALS and, in most families, its inheritance is consistent with an autosomal dominant trait with age-dependent penetrance. The biochemical abnormality underlying the disorder is unknown. We analyzed DNA from 131 members of 6 multigenerational ALS families, which included 13 affected members, for genetic linkage to 39 expressed and DNA markers, using the techniques of 2-point linkage analysis, multilocus linkage analysis, and exclusion mapping. We identified FALS families with structures suitable for linkage, by computer simulation techniques. A DNA bank established to provide optimum use of available FALS families provided DNA from immortalized lymphoblast cell lines and frozen postmortem tissue. We could not link FALS to any of the markers studied, but excluded chromosome regions unlikely to be a locus of the FALS gene. With the help of this exclusion data, we will concentrate on regions of the human genome that remain unexcluded.

Amyotrophic Lateral Sclerosis↗
PubMed1988

The poliovirus sensitivity (PVS) gene is on chromosome 19q12----q13.2.

Sensitivity to nonmodified poliovirus infection is an autosomal dominant trait, specific to primates. The gene for poliovirus sensitivity (PVS) is encoded on human chromosome 19. In order to sublocalize the PVS gene, we infected rodent-human hybrid cell lines that divide human chromosome 19 into four regions with poliovirus 1 and/or 3. When infected, these hybrid cell lines showed the typical cytopathic effect of poliovirus infection only if they contained 19q12----q13.2 as the smallest region of overlap. Appropriate negative and positive controls were used. PVS may be of relevance to myotonic dystrophy (DM) and the inherited motor neuron diseases: to DM because it localizes to the same region of chromosome 19 and to the inherited motor neuron diseases because it encodes a cell-surface receptor expressed on motor neurons.

Cell Line↗
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↗
PubMed1988

Update on the molecular genetics of Duchenne muscular dystrophy.

Three separate lines of evidence led to the assignment of the Duchenne muscular dystrophy (DMD) gene to the 21.2 band on the short arm of the X chromosome. A portion of the putative gene, thought to extend over 1-2 million base pairs has been recently cloned. DNA probes from the Xp21.2 region detect large deletions in 5-20% DMD boys and are presumed to lead to the DMD phenotype in those individuals. Deletions have also been noted in the DNA of patients with Becker muscular dystrophy. These exciting developments have a direct bearing on carrier detection and prenatal diagnosis. Prenatal diagnosis in deletion families approaches greater than 99% accuracy and can be utilized to save 50% of normal male fetuses carried by carrier mothers who would otherwise choose to abort all male fetuses.

Cloning, Molecular↗
PubMed1987

Chorea-acanthocytosis: a report of three new families and implications for genetic counselling.

Chorea-acanthocytosis (CHA) is a rare inherited neurologic disorder with peripheral red cell acanthocytes and normal serum lipoprotein levels. To date, 8 families with the disorder have been reported outside of Japan. We describe 4 patients in 3 families with CHA and review the clinical presentations in previous reports. In addition, we report magnetic resonance imaging scans in these patients. The pattern of inheritance in these families is most likely autosomal recessive. Obligate heterozygotes do not have acanthocytes on wet preparation under phase microscope. Two of 3 propositi were initially diagnosed as having Huntington chorea. Chorea-acanthocytosis is an important differential in the diagnosis of Huntington chorea and should be considered in families without a family history. The paucity of families with CHA reported to date may represent lack of recognition.

Acanthocytes↗
PubMed1985

Autosomal dominant syndrome of lipid neuromyopathy with normal carnitine: successful treatment with long-chain fatty-acid-free diet.

A family (mother and two sons) have had lifelong muscle weakness and intolerance to fatty food. Histochemistry of muscle biopsies of all three patients demonstrated increased lipids in type I muscle fibers and type II muscle fiber atrophy and paucity. Electronmicroscopy of muscle revealed increased lipids, abnormal mitochondria, and increased lipofuscin granules. Electronmicroscopy of sural nerve showed inclusions in most of the Schwann cell cytoplasm, with lipid droplets, zebra bodies, lipofuscin granules, and abnormal mitochondria. Carnitine and CPT I and II levels were normal in serum and muscle. Treatment with long-chain fatty-acid-free diet resulted in remarkable clinical improvement and in decrease of lipid droplets in the muscle. This dietary program may be useful in other forms of lipid myopathy.

Adolescent↗
PubMed1983

Effect on weakness and spasticity in amyotrophic lateral sclerosis of thyrotropin-releasing hormone.

Very high intravenous doses (2-19 mg/min) of thyrotropin-releasing hormone (TRH, L-pyroglutamyl-L-histidyl-L-prolinamide) given to 12 patients with amyotrophic lateral sclerosis (ALS) produced a moderate to marked improvement of functions caused by deficiency of lower motor neurons (weakness) and upper motor neurons (spasticity). The improvement was sustained throughout the infusion and for about 1 h thereafter; sometimes a slight improvement was evident 20 h after infusion. At a given dose benefits and side-effects were more evident in men than in women. Whether TRH is replacing an ALS-associated deficiency or is simply a symptomatic treatment is unknown. The results of this study raise the possibility of a treatment for ALS, and may provide new insight into its pathogenesis. The potential response to TRH of spasticity and/or lower motor neuron involvement of other causes is proposed.

Adult↗
PubMedDate not supplied

A molecular genetic approach to amyotrophic lateral sclerosis.

Disorders of the motor neurons may affect both the upper and lower neurons, primarily the lower motor neurons as in the spinal muscular atrophies are primarily the upper motor neurons as in the familial spastic paraplegias. Amyotrophic lateral sclerosis is a degenerative disorder of the motor neuron that results in paralysis and wasting of voluntary muscles. Large motor neurons in the cerebral cortex, brain stem and spinal cord degenerate or are lost. Hyaline inclusions may be seen in the cytoplasm of surviving motor neurons. Acute axonal degeneration of peripheral motor fibers occurs at all levels, including the distal axon. Subclinical involvement of the spinecerebellar tracts, posterior column and Clarke's column as well as loss of large neurons in the dorsal root ganglia and neurons of oculomotor nuclei has been reported. The average duration of life onset of symptoms of amyotrophic lateral sclerosis is three years and ninety per cent of patients died within 5 years. The basic mechanism of disease in amyotrophic lateral sclerosis remains unknown. There is no known treatment that will prevent, reverse or otherwise alter the course of the disease. Autosomal dominant and autosomal recessive forms of amyotrophic lateral sclerosis are genetic models of amyotrophic lateral sclerosis which may provide insight into the disease mechanism of sporadic amyotrophic lateral sclerosis, five to ten percent of adult cases of amyotrophic lateral sclerosis with early onset of symptoms and a more benign course. It is conceivable that both genetic and sporadic forms of amyotrophic lateral sclerosis result from failure of the same or similar neuronal mechanism triggered by defective genes and by an environment agent in sporadic amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis↗
PubMedDate not supplied

Degeneration of the substantia nigra in familial amyotrophic lateral sclerosis.

We have studied a large family with familial amyotrophic lateral sclerosis (FALS) and examined the brain and spinal cord of a 40-year-old male family member at autopsy three years after clinical onset of the disease. The most unusual finding was a severe degree of neuronal loss of the substantia nigra accompanied by gliosis and numerous pigment-laden macrophages. There was marked degeneration of the upper and lower motor neurons and the corticospinal tracts. In addition, there was an unusually severe degree of diffuse degeneration throughout the anterolateral columns of the spinal cord. The posterior columns and Clarke's nucleus were not involved. Nigral degeneration has rarely been reported in FALS. The findings in this case emphasize the great variability of morphologic changes encountered in FALS and raise the question of a relationship between FALS and extrapyramidal disorders such as Parkinson's disease. We conclude that careful postmortem examinations of further cases of FALS are needed to fully define the extent of degenerative changes in this disease.

Adult↗