A 28-year-old man presents to the emergency room (ER) with a large amount of blood and protein in his urine. He has had a sensorineural hearing loss since his teen years and has misshaped lenses (anterior lenticonus). The physician is suspicious of a genetic disorder that may lead to eventual kidney failure. If this is the case, the patient most likely has a mutation in which one of the following proteins?
The patient has Alport syndrome, a mutation in type IV collagen that alters the basement membrane composition of kidney glomeruli. In the absence of a functional basement membrane, the kidneys have difficulty in properly filtering waste products from blood into the urine, and both blood and proteins can enter the urine. Type IV collagen is also important for hearing (it is found in the inner ear) and for the eye. Type IV collagen forms a mesh-like structure, which is different from the rod-like structures found in type I collagen and is found in almost all basement membrane structures. Given sufficient time, the alteration in the basement membrane in the glomeruli will lead to their destruction and loss of kidney function. A mutation in a1-antitrypsin will lead to emphysema, mutations in spectrin can lead to hereditary spherocytosis, mutations in fibrillin lead to Marfan syndrome, and mutations in b-myosin heavy chain can lead to FHC.
Spectrin
a1-Antitrypsin
Collagen
Fibrillin
Proteins and Amino Acids