00:00 / 00:00
Evolution and natural selection
Independent assortment of genes and linkage
Mendelian genetics and punnett squares
Alagille syndrome (NORD)
Familial adenomatous polyposis
Multiple endocrine neoplasia
Polycystic kidney disease
Treacher Collins syndrome
von Hippel-Lindau disease
Gaucher disease (NORD)
Glycogen storage disease type I
Glycogen storage disease type II (NORD)
Glycogen storage disease type III
Glycogen storage disease type IV
Glycogen storage disease type V
Mucopolysaccharide storage disease type 1 (Hurler syndrome) (NORD)
Niemann-Pick disease type C
Niemann-Pick disease types A and B (NORD)
Primary ciliary dyskinesia
Sickle cell disease (NORD)
Tay-Sachs disease (NORD)
Cri du chat syndrome
Fragile X syndrome
Down syndrome (Trisomy 21)
Edwards syndrome (Trisomy 18)
Patau syndrome (Trisomy 13)
Fabry disease (NORD)
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Mucopolysaccharide storage disease type 2 (Hunter syndrome) (NORD)
Ornithine transcarbamylase deficiency
Autosomal trisomies: Pathology review
Miscellaneous genetic disorders: Pathology review
Muscular dystrophies and mitochondrial myopathies: Pathology review
0 / 16 complete
0 / 5 complete
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.
Latest on COVID-19
Nurse Practitioner (NP)
Physician Assistant (PA)
Create custom content
Raise the Line Podcast
Copyright © 2024 Elsevier, its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
Cookies are used by this site.
Terms and Conditions
USMLE® is a joint program of the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME). COMLEX-USA® is a registered trademark of The National Board of Osteopathic Medical Examiners, Inc. NCLEX-RN® is a registered trademark of the National Council of State Boards of Nursing, Inc. Test names and other trademarks are the property of the respective trademark holders. None of the trademark holders are endorsed by nor affiliated with Osmosis or this website.