A 24-year-old woman comes to the office for a preemployment medical evaluation. The patient has no known medical problems but reports that her skin bruises and scars easily. She says that most of her family members have a very "flexible" body, and her brother works in a circus as a contortionist. The patient takes no medications and has no allergies. She does not use tobacco, alcohol, or drugs. Physical examination findings are shown in the exhibit.

This patient most likely has an inherited defect in which of the following proteins?

Question

A 24-year-old woman comes to the office for a preemployment medical evaluation. The patient has no known medical problems but reports that her skin bruises and scars easily. She says that most of her family members have a very "flexible" body, and her brother works in a circus as a contortionist. The patient takes no medications and has no allergies. She does not use tobacco, alcohol, or drugs. Physical examination findings are shown in the exhibit.

This patient most likely has an inherited defect in which of the following proteins?

Quizplus · Accepted Answer

11ec160b_3699_4bb6_9249_f97fd35549a6_MD0001_00 The extracellular matrix is a network of interstitial proteins that maintain normal tissue architecture. Collagen is a major component of connective tissue and consists of 3 polypeptide ? chains held together by hydrogen bonds to form a ropelike triple helix structure (tropocollagen). Lysyl oxidase then forms covalent bonds between individual tropocollagen molecules, generating mature collagen fibers. The variation in amino acid sequences in the collagen ? chains gives rise to collagen diversity in different tissues. Collagen types I, II, III, and V provide tensile strength in skin, bones, cartilage, tendons, and blood vessels. Ehlers-Danlos syndrome (EDS) is a group of hereditary disorders involving a defect in collagen synthesis. EDS usually manifests clinically as hypermobile joints, overelastic skin, and fragile tissue susceptible to bruising, wounds, and hemarthrosis. Common mutations leading to EDS phenotypes include deficiencies of the lysyl hydroxylase and procollagen peptidase enzymes responsible for collagen synthesis. (Choice B) Elastin, a fibrous protein in the connective tissue, is named for the elastic properties it imparts to skin, blood vessels, and lung alveoli. Elastin fibers can be stretched to several times their original length but will recoil when the stretching forces are withdrawn. Elastin is synthesized from the polypeptide precursor tropoelastin. (Choice C) Fibrillin-1 is a major component of the microfibrils that form a sheath around elastin. Microfibrils are abundantly present in blood vessels and in the suspensory ligaments of the lens. Defects in the fibrillin-1 gene cause classic autosomal dominant Marfan syndrome. (Choice D) Hyaluronic acid is another major component of the soft tissue's extracellular matrix, including synovial fluid and skin. Exogenous injection can be used to restore viscoelasticity to the synovial fluid in osteoarthritis; soft-tissue fillers can also be used in patients concerned about age-related volume loss (eg, nasolabial folds). (Choice E) Laminins are heterotrimeric glycoproteins that bind to type IV collagen underlying epithelial cells. They contribute to the organization and function of the basal lamina (basement membrane). (Choice F) Proteoglycans are composed of glycosaminoglycans (GAGs), which provide compressibility to tissues. Patients with deficiencies in lysosomal enzymes cannot break down GAGs, resulting in mucopolysaccharidoses (eg, Hurler syndrome, Hunter syndrome) characterized by soft tissue and skeletal disease. Educational objective: Ehlers-Danlos syndrome (EDS) is a heritable connective tissue disease associated with abnormal collagen formation. EDS usually manifests clinically as overflexible (hypermobile) joints, overelastic (hyperelastic) skin, and fragile tissue susceptible to bruising, wounding, and hemarthrosis. __________ References: Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type. (http://www.ncbi.nlm.nih.gov/pubmed/20847697) Ehlers-Danlos syndrome: how to diagnose and when to perform genetic tests. (http://www.ncbi.nlm.nih.gov/pubmed/24994860) The Ehlers-Danlos syndrome, a disorder with many faces. (http://www.ncbi.nlm.nih.gov/pubmed/22353005)

A 24-Year-Old Woman Comes to the Office for a Preemployment