Gayle Fiser
Online Mendelian Inheritance in Man Exercise I
6a. Which gene is mutated in individuals with sickle-cell anemia?
A mutant beta globin gene HBB 141900 causes the sickling. A single point mutation that codes for valine instead of glutamic acid is responsible.
6b. What are the major symptoms of this disorder? The major symptoms of this disorder include pain. Pain, which can be categorized as acute (crisis’s) in the chest, abdomen, and joints. Some bone pain could be present. Anemia (low red blood cell count) is another indicator, along with frequent infections due to splenic damage. Babies and young children may have swollen hands and feet, along with delayed growth. Vision problems are also common.
6c. What was the first published scientific description of sickle-cell anemia?
Walter-Clement Noel was the first to be described case of sickle cell anemia in 1910, by J.B. Herrick, Peculiar elongated and sickle-shaped red blood corpuscles in a case of sever anemia in the Yale Journal of Biology and Medicine.
Here are images of the sickling red blood cells.
Below is a snapshot of a portion of the report by Jessie Schriver, M.D. and T.R. Waugh, M.D. in September, 1930. A seven year old patient had presented with cough, night sweats, pains in legs and joints, abdominal pain, poor appetite and increasing fatigue. In their experimentation, they found sickling occurred when oxygen pressures fell below 40 to 45.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC382053/pdf/canmedaj00096-0043.pdf
6d. Describe two other features of this disorder that you learned from the OMIM database and state where in the database you found this information.
Before I became a teacher, I was an Emergency Department Registered Nurse. I had patients that were in sickle-cell crisis, presenting with shortness of breath and pain. Most of my experience is in the treatment of those acute symptoms. I found the topics of increased osteonecrosis and gallstones in sickle cell disease interesting.
Osteonecrosis: A link from the references of the OMIM entry lead me to:
http://www.nejm.org/doi/full/10.1056/NEJM199111213252104
The New England Journal of Medicine
Sickle Cell Disease as a Cause of Osteonecrosis of the Femoral Head
There is an increased incidence of osteonecrosis of the femoral head with patients that have more frequent vasocclusion crises. Joint replacement is an option.
Gallstones: A link from the references of the OMIM entry lead me to:
http://www.jpeds.com/article/S0022-3476(00)90054-4/abstract
The Journal of Pediatrics
There is a high incidence of gallstones.
Other topics of interest: Problems with those with the trait, including physical activity and high altitudes.
Exercise II – A Dominant Disorder – Marfan Syndrome
(This disorder was chosen to learn more about Marfan Syndrome. My students were very familiar with basketball player, Chris Weisheit)
6a. Which gene is mutated in individuals with Marfan Syndrome?
The FBN1 gene is responsible for making fibrillin-1 which works with other fibrillin-1 to make microfibrils which give strength and flexibility to connective tissues. A mutation in this gene is responsible for this multiple organ syndrome.
6b. What are the major symptoms of this disorder?
The disorder causes loss of strength and flexibility of the connective tissue and an increased production of growth factors in these cells.
The main symptoms patients present with are a displacement of the lens from the center of the pupil, disproportionate extremities, dilation of the aorta, which is a predisposition for an aortic tear or rupture.
These three systems are the cardinal features: skeletal, cardiovascular, and ocular
6c. What was the first published scientific description of Marfan Syndrome?
The syndrome was named by Antoine Marfan in 1896. His patient was a 5.5 year old girl, named Gabriella P. His article:
Marfan, Antoine (1896). "Un cas de déformation congénitale des quartre membres, plus prononcée aux extrémitiés, caractérisée par l'allongement des os avec un certain degré d'amincissement" Bulletins et memoires de la Société medicale des hôspitaux de Paris 13 (3rd series): 220–226.
Translation: A case of congenital deformation of the four limbs, more pronounced at the extremities, characterized by elongation of the bones with some degree of thinning.
6d. Describe two other features of this disorder that you learned from the OMIM database and state where in the database you found this information. Information found in the references on OMIM:
Not all symptoms are present in all cases:
Homozygosity for autosomal dominant Marfan syndrome.
Journal of Medical Genetics
http://jmg.bmj.com/content/21/3/173.long
A pedigree from the article:
What does this look like? Pictures from an another article found on OMIM, Marfan Syndrome, also in the Journal of Medical Genetics.
http://jmg.bmj.com/content/33/5/403.long