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Amyotrophic lateral sclerosis
von Hippel-Lindau disease
Acoustic neuroma (schwannoma)
Adult brain tumors
Pediatric brain tumors
Transient ischemic attack
Cavernous sinus thrombosis
Spinocerebellar ataxia (NORD)
Tethered spinal cord syndrome
Lewy body dementia
Normal pressure hydrocephalus
Acute disseminated encephalomyelitis
Central pontine myelinolysis
JC virus (Progressive multifocal leukoencephalopathy)
Idiopathic intracranial hypertension
Opsoclonus myoclonus syndrome (NORD)
Restless legs syndrome
Early infantile epileptic encephalopathy (NORD)
Cauda equina syndrome
Treponema pallidum (Syphilis)
Vitamin B12 deficiency
Concussion and traumatic brain injury
Spinal muscular atrophy
Carpal tunnel syndrome
Thoracic outlet syndrome
Lambert-Eaton myasthenic syndrome
Adult brain tumors: Pathology review
Central nervous system infections: Pathology review
Cerebral vascular disease: Pathology review
Congenital neurological disorders: Pathology review
Dementia: Pathology review
Demyelinating disorders: Pathology review
Headaches: Pathology review
Movement disorders: Pathology review
Neurocutaneous disorders: Pathology review
Neuromuscular junction disorders: Pathology review
Pediatric brain tumors: Pathology review
Seizures: Pathology review
Spinal cord disorders: Pathology review
Traumatic brain injury: Pathology review
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Huntington's Disease & 5 Girls
Creutzfeldt-Jakob Disease, Parkinson's Disease & Huntington's Disease
Huntington disease p. 536
basal ganglia lesions p. 526
neurodegenerative disorder p. 536
neurotransmitters for p. 508
ventromegaly p. 538
Huntington disease, or HD, is a rare neurodegenerative disease that involves a repeated sequence of DNA that causes an abnormal protein to form, leading to abnormal movements and cognitive problems.
Huntington disease is an autosomal dominant genetic disorder, which means that one affected copy of a gene is enough to cause disease. Affected people are typically present in each generation, because an affected person (male or female) has a 50% chance of passing on the affected gene to a child, which causes that child to have the disease.
In most people, a gene called huntingtin or HTT on chromosome 4, contains a triplet repeat, where the nucleotides C, A, and G are repeated 10-35 times in a row. In people with Huntington disease, this repeat goes on for 36 or more times in a row. CAG codes for the amino acid glutamine, so people with Huntington disease patients will have 36 or more glutamines in a row in the huntingtin protein. So, in addition to being a triplet repeat disorder, HD is, more specifically, a “polyglutamine” disease.
The specific way in which extra glutamines cause HD symptoms isn’t fully worked out, but some clues are that the mutated protein aggregates within the neuronal cells of the caudate and putamen of the basal ganglia causing neuronal cell death. Cell death might be related to excitotoxicity – which is excessive signaling of these neurons, which leads to high intracellular calcium.
The expanded CAG repeats not only affect the huntingtin protein – they affect DNA replication itself. When copying the HTT gene, DNA polymerase can basically lose track of which CAG it’s on and accidently add extra CAGs. Since as a zygote develops into a fetus and eventually into a full adult, by the time sperm and eggs are created, several dozen cell divisions, each with a round of DNA replication have taken place, and so there have already been ample opportunities for repeat expansion, and the more repeats that’re added, the more unstable it gets.
This expansion of the originally inherited gene means a child of a parent with HD can inherit even more CAG repeats than the parent did. The higher the number of repeats in the protein, the earlier the age when a person starts having symptoms. This phenomenon is called anticipation, which means that Huntington disease families often show earlier symptom onset with each generation. Even repeats of 27-35 CAGs can expand occasionally; these are called “pre-mutation” alleles, since they don’t cause the disease, but they’re set-up for developing a mutation of 36 or more CAGs.
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