A six month old baby girl who was normal at bih, begins to show signs of motor retardation. While she could sit up at 5 months, she can no longer do so. As time goes on, the child continues to deteriorate, and eventually becomes unresponsive to visual or auditory stimuli. Funduscopic examination reveals cherry-red macular spots in both eyes. Which of the following genetic abnormalities is most often related to the development of this disease?
Most cases of Tay-Sachs disease are caused by inseion of four nucleotides into the coding region of the gene for the alpha-subunit of the hexosaminidase A gene. This produces a frameshift mutation, resulting in the creation of a premature stop codon downstream from the inseed nucleotides. The disease presents as described in the question, and is more common in Ashkenazi Jews. The carrier rate in this population is 1 in 25. There is presently no effective treatment and survival beyond four years of age is rare. Confined placental mosaicism is caused by a genetic aberration (e.g., a trisomy) occurring in the trophoblast or extraembryonic progenitor cells in the inner cell mass of the embryo. This leads to abnormal placental development and intrauterine growth retardation. Expansion of tandem nucleotide repeats is thought to be etiologically involved in Fragile X syndrome and Huntington disease. Nondisjunction during meiosis is a common cause of trisomy, e.g., trisomy 21, or Down syndrome. Ref: Wyatt C., Kemp W.L., Moos P.J., Burns D.K., Brown T.G. (2008). Chapter 6. Genetic Disorders. In C. Wyatt, W.L. Kemp, P.J. Moos, D.K. Burns, T.G. Brown (Eds), Pathology: The Big Picture.
Confined placental mosaicism
Expanded trinucleotide repeat
Frameshift mutation
Nondisjunction