Biochem - Genetics (Autosomal-dominant diseases) Flashcards
Pg. 87 in First Aid 2014 Sections include: -Autosomal dominant diseases
What was the former name of Autosomal dominant polycystic kidney disease (ADPKD)?
Formerly known as adult polycystic kidney disease
What is the main presentation of ADPKD, and what causes this?
Always bilateral, massive enlargement of kidneys due to multiple large cysts
What mutations cause ADPK? On what chromosomes are they? What percentage of cases are attributed to each of these?
85% of cases are due to mutation in PKD1 (chromosome 16; Think: “16 letters in polycystic kidney”); Remainder due to mutation in PKD2 (chromosome 4)
What defines familial adenomatous polyposis, and when does it occur?
Colon becomes covered with adenomatous polyps after puberty
To what does familial adenomatous polyposis progress? How is this progression prevented?
Progresses to colon cancer unless colon is resected
What mutation and chromosome are associated with familial adenomatous polyposis?
Mutations on chromosome 5 (APC gene); Think: “5 letters in ‘polyp’”
What is the defect in familial hypercholesterolemia, and what effect does it have?
Elevated LDL due to defective or absent LDL receptor
What are the 2 main clinical findings caused by familial hypercholesterolemia?
Leads to severe atherosclerotic disease early in life, and tendon xanthomas (classically in the Achilles tendon)
What is Hereditary hemorrhagic telangiectasia? What is another name for it?
Inherited disorder of blood vessels; Also known as Osler-Weber-Rendu syndrome
What are 6 clinical findings associated with hereditary hemorrhagic telangiectasia?
Findings: (1) telangiectasia (2) recurrent epistaxis (3) skin discolorations (4) atriovenous malformations (AVMs) (5) GI bleeding (6) hematuria
What is the defect in hereditary spherocytosis, and what effect does it have?
Spheroid erythrocytes due to spectrin or ankyrin defect
What are 2 clinical/lab findings associated with hereditary spherocytosis?
Hemolytic anemia; high MCHC
What is the treatment for hereditary spherocytosis?
Treatment: splenectomy
What are 5 clinical/lab findings associated with Huntington disease?
Findings: (1) depression, (2) progressive dementia, (3) choreiform movements, (4) caudate atrophy, and (5) low levels of GABA and ACh in the brain
On what chromosome is the Huntington gene?
Gene on chromosome 4; Think: “Hunting 4 food”
What kind of repeats are associated with Huntington disease? What effect do increasing number of repeats have?
Trinucleotide repeat disorder: (CAG)n. Increased repeats –> Decreased age of onset
What is the defect in Marfan syndrome, and what effects does it have?
Fibrillin-1 gene mutation –> connective tissue disorder affecting skeleton, heart, and eyes
What are 4 physical findings associated with Marfan syndrome?
Findings: (1) tall with long extremities (2) pectus excavatum (3) hypermobile joints (4) Long, tapering fingers and toes (arachnodactyly)
What aortic finding is associated with Marfan syndrome, and what causes it?
Cystic medial necrosis of aorta –> aortic incompetence and dissecting aortic aneurysms
What cardiac finding is associated with Marfan syndrome?
Floppy mitral valve
What ocular finding is associated with Marfan syndrome?
Subluxation of lenses, typically upward and temporally
What is MEN, and what are the types of MEN? In general, what characterizes them?
Multiple endocrine neoplasias (MEN); Several distinct syndromes (1, 2A, 2B) characterized by familial tumors of endocrine glands, including those of the pancreas, parathyroid, pituitary, thyroid, and adrenal medulla.
Which what gene is MEN 2A associated? What other type of MEN is also associated with this gene?
MEN 2A and 2B are associated with ret gene
What is another name for Neurofibromatosis type 1?
Neurofibromatosis type 1 (von Recklinghausen disease)
What is Neurofibromatosis type 1, and what 2 main physical findings characterize it?
Neurocutaneous disorder characterized by cafe-au-lait spots and cutaneous neurofibromas
What is the mode of inheritance, penetrance, and expression of neurofibromatosis type 1?
Autosomal dominant, 100% penetrance, variable expression
What gene mutations cause Neurofibromatosis type 1, and on what chromosome is the gene found?
Caused by mutations in the NF1 gene on chromosome 17; Think: “17 letters in ‘von Recklinghausen’”
What are 4 clinical findings associated with Neurofibromatosis type 2?
Findings: (1) bilateral acoustic schwannomas (2) juvenile cataracts (3) meningiomas (4) ependymomas
What gene mutations cause Neurofibromatosis type 2, and on what chromosome is the gene found?
NF2 gene on chromosome 22; Think: “type 2 = 22”
What is Tuberous sclerosis, and what finding characterizes it?
Neurocutaneous disorder with multi-organ system involvement, characterized by numerous benign hamartomas
What is the penetrance and expression of Tuberous sclerosis?
Incomplete penetrance, variable expression
What characterizes von Hippel-Lindau disease?
Disorder characterized by development of numerous tumors, both benign and malignant
With what mutation is von Hippel-Lindau disease associated, and on what chromosome is this gene found?
Associated with deletion of VHL gene (tumor suppressor) on chromosome 3 (3p); Think: “Von Hippel-Lindau = 3 words for chromosome 3”
