Problem
Case Study: Adapted from Genetics in Medicine
A.Y., a 6-year-old boy, was referred for mild developmental delay. He had difficulty climbing stairs, running, and participating in vigorous physical activities and decreased strength and endurance. His parents, two brothers, and one sister were all healthy. His mother has two unaffected sisters, each of whom has a healthy son and daughter.
On examination, he had difficulty jumping onto the examination table, a Gowers sign (a sequence of maneuvers for rising from the floor, proximal weakness, a waddling gait, tight heel cords, and enlarged calf muscles. His serum creatine kinase level was 50-fold higher than usual. Because the history, physical examination findings, and elevated creatine kinase level strongly suggested a myopathy, A.Y. was referred to the neurogenetics clinic for further evaluation.
Results of his muscle biopsy showed a marked variation of muscle fiber size, fiber necrosis, fat and connective tissue proliferation, and no staining for dystrophin. Based on these results, A.Y. was given a provisional diagnosis of Duchenne muscular dystrophy, and he was tested for deletions of the dystrophin gene; he was found to have a deletion of exons 45 through 48.
A. Draw the pedigree with all family members identified in the scenario above.
B. What are the possible genotypes of his parents and siblings?
C. If a mutation had not been identified in the boy, are there any other ways to determine if the mother is also a carrier other than genetic testing?
A further review of the family history reveals that his mother also had an uncle on her mother's side that had been in a wheelchair and died at the age of 20 due to respiratory failure.
D. How does this change the likelihood that the boy's mother is a DMD carrier?