The parents of a 3-year-old boy bring him to the hospital following a fall as they are concerned he has broken his arm. His parents report that over the past year he has had several episodes of what they think is uncharacteristically easy fractures in his legs from minor falls. They indicate that there is no family history of bone disease. Physical examination shows bowing and deformities of the legs, and x-rays show evidence of previous fractures and osteopenia. The physician suspects a collagen defect and orders a skin biopsy. The results of the biopsy show unstable type I collagen that is due to a single-point mutation in one of the type I genes. This mutation is most likely caused by which of the following amino acid substitutions in this patient?

Question

Quizplus · Accepted Answer

Glycine is critical in the collagen triple helix structure, and its substitution with a bulkier amino acid like leucine can disrupt the structure, leading to conditions like osteogenesis imperfecta.  The triple-helical structure of collagen arises from an unusual abundance of 3 amino acids: glycine, proline, and hydroxyproline. These amino acids make up the characteristic repeating motif Gly-Pro-X, where X can be any amino acid. The side chain of glycine, an H atom, is the only one that can fit into the crowded center of a 3-stranded helix. Hydrogen bonds linking the peptide bond nitrogen of a glycine residue with a peptide carbonyl group in an adjacent polypeptide help hold the 3 chains together. It is because of this role of glycine in collagen that it is indispensable for normal collagen structure and function. Therefore, a mutation causing a substitution of glycine for leucine would result in the production of defective collagen.

The Parents of a 3-Year-Old Boy Bring Him to the Hospital