Hereditary leukodystrophies without identified mutations.
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Adult↗
Biomedical subjects
Yves Robitaille
Publications and source records attributed to Yves Robitaille.
Sudden death in growth hormone-treated children with Prader-Willi syndrome.
A 4-year-old boy with Prader-Willi syndrome died suddenly while asleep on day 67 of growth hormone treatment. During treatment, snoring had worsened. Autopsy showed multifocal bronchopneumonia. This case and two others recently published suggest that growth hormone may be associated with obstructive apnea, respiratory infection, and sudden death in this condition.
Bronchopneumonia↗
TAU mutations are not a predominant cause of frontotemporal dementia in Canadian patients.
OBJECTIVE: Frontotemporal dementia is a neurodegenerative disease affecting mostly the frontal and/or temporal lobes, with neuronal loss and intraneuronal and/or intraglial inclusions composed of hyperphosphorylated microtubule-associated protein tau and ubiquitin. Missense and splice site mutations in the TAU gene have been identified in approximately 15% of all frontotemporal dementia cases. In this study, we evaluated the involvement of mutations in the TAU gene in development of frontotemporal dementia phenotype in patients of French or English Canadian origins. METHODS: Fourteen patients with frontotemporal dementia phenotype and 98 normal controls were recruited for the study. The TAU gene was screened by sequencing and denaturing high performance liquid chromatography. RESULTS: No mutations, except some new polymorphisms, were detected in the TAU gene of these patients. One polymorphism, however, may play a role in pathogenesis. CONCLUSION: Our results agree with previous work suggesting that mutations in this gene are not a frequent cause of the frontotemporal dementia phenotype in Canadian patients.
Canada↗
hTERT gene amplification and increased mRNA expression in central nervous system embryonal tumors.
High-level gains at 5p15, a chromosomal region including the human telomerase catalytic protein subunit (hTERT) gene, have been documented in several medulloblastomas. We therefore analyzed hTERT gene dosage in a group of medulloblastomas and other embryonal brain tumors using differential PCR. Amplification of the hTERT locus was detected in 15 of 36 (42%) tumors examined. To correlate gene amplification with message level, we used real-time quantitative PCR to measure hTERT mRNA in 50 embryonal brain tumors. hTERT mRNA was detected in all but one of these cases, and mRNA level correlated significantly with gene dosage (r = 0.82). Log-rank analysis of survival data revealed a trend toward poor clinical outcomes in patients with medulloblastomas containing high hTERT mRNA levels, but clinical follow-up was relatively short and the association was not statistically significant (P = 0.078). Comparative genomic hybridization was used to further analyze the tumor with the greatest hTERT gene dosage and mRNA level, a recurrent medulloepithelioma. hTERT was amplified in the recurrent tumor but not in the primary lesion, suggesting this locus can be involved in tumor progression. Our data indicate that hTERT gene amplification is relatively common in embryonal brain tumors, and that increased expression of hTERT mRNA may be associated with biologically aggressive tumor behavior.
Adolescent↗
Bilateral Rasmussen encephalitis: postmortem documentation in a five-year-old.
A case of Rasmussen encephalitis with bilateral involvement and onset at age 2 years is reviewed. Rasmussen encephalitis is a rare progressive disease that causes intractable seizures, cognitive decline, and inflammatory changes in the brain. The neurologic involvement is characteristically unilateral. Bilateral involvement in this case was suspected within 5 months of presentation and was confirmed by bilateral frontal lobe biopsies. The severity and progression of the disease in this case was remarkable and resulted in the patient's death by age 5 years, despite numerous attempted therapeutic interventions. Autopsy findings confirmed the diagnosis of Rasmussen encephalitis with bilateral involvement.
Atrophy↗
Declining expression of neprilysin in Alzheimer disease vasculature: possible involvement in cerebral amyloid angiopathy.
Molecular, genetic, and pharmacological studies have shown that neprilysin (also called NEP) catabolizes amyloid beta peptides (A beta) in healthy conditions. However, in Alzheimer disease (AD), A beta accumulates forming senile plaques in brain parenchyma and amyloid deposition around blood vessels. In this study, we tested at cellular level the relationship between neprilysin and A beta in human healthy and AD brain. Our results provided evidence for declining levels of neprilysin in AD brains as compared to healthy controls in parallel with increasing deposition of A beta. In hippocampus of AD individuals we observed a significant down-regulation of neprilysin expression in pyramidal neurons, consistent with the possibility that neprilysin controls the level of A beta accumulation and plaque formation in this area. In the cortex and leptomeninges, neprilysin was expressed in the smooth muscle cells of blood vessels. In sections from AD patients we observed a clear inverse relationship between neprilysin and A beta peptide levels in the vasculature, implicating neprilysin in cerebral amyloid angiopathy.
Alzheimer Disease↗
Pelizaeus-Merzbacher disease.
Pelizaeus-Merzbacher disease (PMD) can now be defined as an X-linked recessive leukodystrophy that is caused by a mutation in the proteolipid protein (PLP) gene on chromosome Xq22. The most common mutation is gene duplication followed in frequency by missense mutations, insertions, and deletions. The clinical spectrum ranges from severe neonatal cases to relatively benign adult forms and X-linked recessive spastic paraplegia type 2. The lack of PLP is accompanied by deficits in the other myelin proteins of the central nervous system, including myelin basic protein, myelin-associated glycoprotein, and cyclic nucleotide phosphodiesterase. Surprisingly, the total absence of PLP due to gene deletion or a null allele causes a relatively benign form of PMD. Abnormal PLP is thought to impair protein trafficking and to induce apoptosis in oligodendroglia. Immunocytochemistry with specific antibodies reveals the PLP deficiency and insufficient generation of myelin sheaths with the remaining proteins. Both excessive biosynthesis of PLP, as in gene duplications, or conformational change of the protein, as in missense mutations, are detrimental to myelination. Several naturally occurring and transgenic animal models with PLP gene mutations or deletions have contributed to our understanding of dysmyelination in PMD and the general knowledge of myelination and myelin repair.
Animals↗