PubMed Health⌕ Search

Biomedical subjects

P J Lamont

Publications and source records attributed to P J Lamont.

10 recordsLinked to original sources
PubMed2005

Laing early onset distal myopathy: slow myosin defect with variable abnormalities on muscle biopsy.

BACKGROUND: Laing early onset distal myopathy (MPD1) is an autosomal dominant myopathy caused by mutations within the slow skeletal muscle fibre myosin heavy chain gene, MYH7. It is allelic with myosin storage myopathy, with the commonest form of familial hypertrophic cardiomyopathy, and with one form of dilated cardiomyopathy. However, the clinical picture of MPD1 is distinct from these three conditions. OBJECTIVE: To collate and discuss the histological features reported in the muscle biopsies of MPD1 patients and to outline the clinical features. RESULTS: The phenotype of MPD1 was consistent, with initial weakness of great toe/ankle dorsiflexion, and later development of weakness of finger extension and neck flexion. Age of onset was the only variable, being from birth up to the 20 s, but progression was always very slow. The pathological features were variable. In this retrospective series, there were no pathognomonic diagnostic features, although atrophic type I fibres were found in half the families. Rimmed vacuoles are consistently seen in all other distal myopathies with the exception of Myoshi distal myopathy. However, they were found in a minority of patients with MPD1, and were not prominent when present. Immunohistochemical staining for slow and fast myosin showed co-expression of slow and fast myosin in some type I fibres, possibly indicating a switch to type II status. This may be a useful aid to diagnosis. CONCLUSIONS: The pathological findings in MPD1 are variable and appear to be affected by factors such as the specific muscle biopsied, the age of the patient at biopsy, and the duration of disease manifestations.

Adolescent↗
PubMed2004

Nemaline rods and complex I deficiency in three infants with hypotonia, motor delay and failure to thrive.

Three infants are described who had nemaline rods on muscle biopsy and isolated deficiency of complex I of the respiratory chain on biochemical analysis. They all manifested failure to thrive from birth, and hypotonia and muscle weakness within the first three months of life. Different genetic defects leading to isolated complex I deficiency have been described associated with a variety of morphological changes on muscle biopsy, but rods have not been described. Nemaline rods have been secondary phenomena in a number of conditions, as well as being the primary abnormality in nemaline myopathy. However, the combination of nemaline rods and complex I deficiency is an association not previously reported.

Electron Transport Complex I↗
PubMed1999

An mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II gene results in lower levels of the protein and a mitochondrial encephalomyopathy.

A novel heteroplasmic 7587T-->C mutation in the mitochondrial genome which changes the initiation codon of the gene encoding cytochrome c oxidase subunit II (COX II), was found in a family with mitochondrial disease. This T-->C transition is predicted to change the initiating methionine to threonine. The mutation load was present at 67% in muscle from the index case and at 91% in muscle from the patient's clinically affected son. Muscle biopsy samples revealed isolated COX deficiency and mitochondrial proliferation. Single-muscle-fiber analysis revealed that the 7587C copy was at much higher load in COX-negative fibers than in COX-positive fibers. After microphotometric enzyme analysis, the mutation was shown to cause a decrease in COX activity when the mutant load was >55%-65%. In fibroblasts from one family member, which contained >95% mutated mtDNA, there was no detectable synthesis or any steady-state level of COX II. This new mutation constitutes a new mechanism by which mtDNA mutations can cause disease-defective initiation of translation.

Adult↗
PubMed1998

Fifty year follow-up of a patient with central core disease shows slow but definite progression.

The follow-up of a patient with central core disease (CCD) over 50 years showed that although initially the condition was moderately non-progressive, progression of a significant degree did eventually occur. Histopathological and electron microscopic data were available from muscle biopsies carried out at the ages of 19 and 55 years, and show a marked predominance of type 1 fibres with central cores in most fibres at both ages. The four mutations within the RYR1 gene described in association with CCD and three of the more common malignant hyperthermia-associated mutations within RYR1 were not present.

DNA↗
PubMed1998

Clinical and laboratory findings in referrals for mitochondrial DNA analysis.

BACKGROUND: Increasingly, mutations of mitochondrial DNA (mtDNA) are being considered when investigating the aetiology of neurological diseases in childhood. However, they are often difficult to predict clinically. METHOD: Mitochondrial DNA analysis was carried out on 190 children from 1992 to 1996. Most patients were screened for large scale rearrangements and point mutations at nucleotide positions 3243, 3271, 8344, and 8993. RESULTS: Mutations were found in only 15 patients (7.9%) and were either large scale rearrangements (seven patients) or point mutations at nucleotide position 3243 (eight patients). Other point mutations were screened for depending on the clinical picture. The age of symptom onset was significantly older in children with an mtDNA mutation (mean 7.0 years) compared with children without a mutation (mean 2.8 years). Neither Leigh's syndrome (28 cases) nor severe infantile lactic acidosis (12 cases) was associated with mtDNA mutation. Only three clinical features were significantly associated with an mtDNA mutation: progressive external ophthalmoplegia, myopathy, and pigmentary retinopathy. Family history was valuable: the point mutation at nucleotide 3243 (but not the large scale rearrangements) was associated with maternal inheritance; and consanguinity was not associated with mtDNA mutations. The only investigation that provided specific evidence of an underlying mtDNA mutation was histochemical staining of muscle biopsy specimens. The large scale mutations associated with Kearns-Sayre syndrome and progressive external ophthalmoplegia were found in DNA from muscle only, not leucocyte DNA; whereas point mutations were found in leucocyte DNA. CONCLUSIONS: Even among children seen at a neurogenetic referral centre, mtDNA mutations were very uncommon. Muscle biopsy was the only investigation to provide evidence of mtDNA abnormality.

Acidosis, Lactic↗
PubMed1997

Identification and sizing of the GAA trinucleotide repeat expansion of Friedreich's ataxia in 56 patients. Clinical and genetic correlates.

Fifty-six patients with a clinical diagnosis of Friedreich's ataxia were investigated for the GAA trinucleotide repeat expansion recently found within the gene X25 on chromosome 9. All 56 were found to be homozygous for the expansion, with all but two patients having alleles of differing sizes. The expansion size ranged from 2 to 5 kb, with normal alleles around 1.5 kb. Sizing of the single copy of the expansion in eight sets of parents revealed marked instability in the transmission of the expansion, with both increases and decreases in allele size seen. In Friedreich's ataxia patients there was a significant inverse correlation seen between the average of the two expansions sizes and age of onset of symptoms. The GAA repeat expansion was found in the homozygous state in atypical cases of Friedreich's ataxia, such as older age of onset, preservation of lower limb reflexes and cardiac presentations. In three families the father had onset of spinocerebellar ataxia as an adult, and in two the possibility of partial expression in heterozygote carrier fathers has been raised. More importantly, the history of an ataxic syndrome in a parent does not exclude the diagnosis of Friedreich's ataxia in the offspring, and tests for the expansion should be carried out. The third family with an affected father conforms to previously described 'pseudodominant' inheritance.

Adolescent↗
PubMed1997

Pearson's syndrome without marrow involvement.

A child with a mitochondrial DNA deletion who presented with pancreatic exocrine insufficiency is reported. Though she developed many other features of Pearson's syndrome, there was no bone marrow involvement. Syndromes associated with mitochondrial DNA defects are highly variable and absence of one feature should not inhibit investigation.

Blotting, Southern↗
PubMed1997

A mitochondrial DNA tRNA(Val) point mutation associated with adult-onset Leigh syndrome.

Subacute necrotizing encephalomyelopathy (Leigh syndrome) is associated with a number of mitochondrial DNA (mtDNA) abnormalities. We studied a family with maternally inherited encephalomyelopathy. Two siblings developed adult-onset Leigh syndrome. Muscle biopsy specimens showed enhanced succinic dehydrogenase activity and cytochrome oxidase-negative fibers. We sequenced the ATPase- and transfer RNA (tRNA)-encoding genes of mtDNA and identified a novel mtDNA valine tRNA mutation at base pair 1644. This transversion was heteroplasmic in blood and muscle in all individuals studied, and the proportion of mutant mtDNA correlated with disease severity. This is the first heteroplasmic transversion within a mtDNA tRNA gene and the second pathogenic mtDNA tRNA(Val) mutation to be associated with human disease.

Adult↗
PubMed1991

Plasmapheresis in children with Guillain-Barré syndrome.

Between 1987 and 1989, we plasmapheresed six children with Guillain-Barré syndrome (GBS). None of the children could walk independently at the start of the treatment, and one was being ventilated. Five patients showed clinical improvement during pheresis, and no significant side effects occurred. The median time from onset of weakness to independent walking for these six children was 17 days. This compares with 43 days for 18 children with GBS in this institution who were given supportive measures only.

Adolescent↗